Simple and efficient procedure for the synthesis of symmetrical bis-schiff bases of 5,5'-methylenebis(2-aminothiazole) under solvent-free conditions

Article abstract of DOI:10.1080/00397910903277896

A simple and efficient procedure for the synthesis of symmetrical bis-Schiff bases has been described that employs a condensation reaction of symmetrical primary bis-amine of 5,5'-methylenebis(2-aminothiazole) with a series of aromatic aldehyde derivatives under solvent-free conditions at elevated temperature. The advantages of these reactions are simplicity of the reaction procedure, short reaction times, simple workup, catalyst-free conditions, and pure products in good to excellent yields. Details of the reaction conditions are discussed. Taylor & Francis Group, LLC.

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Simple and Efficient Procedure for the
Synthesis of Symmetrical Bis-Schiff Bases
of 5,5′-Methylenebis(2-aminothiazole)
Under Solvent-Free Conditions
Abbas Shockravi a , Mahdieh Sadeghpour b & Abolfazl Olyaei c
a Faculty of Chemistry, Tarbiat Moallem University , Tehran, Iran
b Department of Chemistry , Islamic Azad University , Takestan
Branch, Qazvin, Iran
c Department of Chemistry , Payame Noor University (PNU) , Qazvin,
Iran
Published online: 05 Aug 2010.
To cite this article: Abbas Shockravi , Mahdieh Sadeghpour & Abolfazl Olyaei (2010) Simple and
Efficient Procedure for the Synthesis of Symmetrical Bis-Schiff Bases of 5,5′-Methylenebis(2-
aminothiazole) Under Solvent-Free Conditions, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 40:17, 2531-2538, DOI:
10.1080/00397910903277896
To link to this article: http://dx.doi.org/10.1080/00397910903277896
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Synthetic Communications1, 40: 2531–2538, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903277896
SIMPLE AND EFFICIENT PROCEDURE FOR THE
SYNTHESIS OF SYMMETRICAL BIS-SCHIFF BASES
OF 5,5’-METHYLENEBIS(2-AMINOTHIAZOLE) UNDER
SOLVENT-FREE CONDITIONS
Abbas Shockravi,1 Mahdieh Sadeghpour,2 and
Abolfazl Olyaei3
1Faculty of Chemistry, Tarbiat Moallem University, Tehran, Iran
2Department of Chemistry, Islamic Azad University, Takestan Branch,
Qazvin, Iran
3Department of Chemistry, Payame Noor University (PNU), Qazvin, Iran
A simple and efficient procedure for the synthesis of symmetrical bis-Schiff bases has been
described that employs a condensation reaction of symmetrical primary bis-amine of
5,50-methylenebis(2-aminothiazole) with a series of aromatic aldehyde derivatives under
solvent-free conditions at elevated temperature. The advantages of these reactions are
simplicity of the reaction procedure, short reaction times, simple workup, catalyst-free
conditions, and pure products in good to excellent yields. Details of the reaction conditions
are discussed.
Keywords: Aldehyde; bis-amine; Schiff bases; solvent-free; symmetrical
INTRODUCTION
Organic reactions under solvent-free or so-called solventless conditions have
gained in popularity in recent years.[1] This is because solvent-free reactions usually
have shorter reaction times, simpler reactors, and simple and efficient workup
procedures. The development of cleaner technologies is an important discussion in
green chemistry. Among the several aspects of green chemistry, the reduction or
replacement of volatile organic solvents from the reaction medium is the most
important. The solid-state reaction or solvent-free reaction has many advantages:
reduced pollution, low cost, and simplicity in process and handling. These factors
are especially important in industry.[2]
Schiff base ligands are widely studied because of physiological, pharmacologi-
cal, and medicinal activities.[3–5] They constitute an interesting class of chelating
agents.[6–8] These complexes are used in some chemical processes as catalysts and
also as biological models in understanding the structure of biomolecules and biological
processes.[9–11]
Received June 30, 2009.
Address correspondence to Abbas Shockravi, Faculty of Chemistry, Tarbiat Moallem University,
Mofatteh Ave., No. 49, Postal Code 15614, Tehran, Iran. E-mail: Abbas_shockravi@yahoo.co.uk
2531

2532
A. SHOCKRAVI, M. SADEGHPOUR, AND A. OLYAEI
A variety of investigations have concerned the synthesis of Schiff bases, but
these methods have some limitations such as use of a high-boiling-point volatile
organic solvent, poor yields, long reaction times, and tedious workup proce-
dures.[12,13] In recent years, synthetic methods have received considerable attention,
and some solvent-free protocols have been developed. Catalyzed synthesis of imines
under solvent-free conditions may be carried out by using microwave irradiation,
ionic liquids, clays, zeolites, silica, alumina, or other matrices.[14]
Particular attention has been paid to the synthesis and study of bis-imine Schiff
bases because of their applications in metal ion complexation and because they can
act as inhibitors of human a-thrombin and microbicides.[15–18] In continuation of our
interest in the synthesis of bis-imine Schiff bases, we decided to synthesize some new
bis-Schiff bases from 5,50-methylenebis(2-aminothiazole)[19] and aromatic aldehydes
using a condensation reaction under solvent- and catalyst-free conditions.
RESULTS AND DISCUSSION
We have previously reported a simple synthesis of bis-Schiff bases by condensation
of 5,50-methylenebis (2-aminothiazole) (1) and aromatic aldehydes (2-hydroxy benzal-
dehyde, 5-bromo-2-hydroxy benzaldehyde, 2-hydroxy-5-nitro benzaldehyde, 4-bromo
benzaldehyde, 3-nitro benzaldehyde, and 2-thiophene carbaldehyde) by reaction in
methanol and formic acid catalyst at room temperature.[20] This method has some limita-
tions such as poor yields, methanol as organic solvent, formic acid as catalyst, and long
reaction times. Based on these facts, we decided to synthesize these bis-Schiff bases and
some new bis-Schiff bases of 5,50-methylenebis(2-aminothiazole) cleanly and efficiently,
without using any acid catalyst, in short reaction times under solventless conditions.
As the model reaction, we initially examined condensation of bis-amine (1)
with 2-hydroxy benzaldehyde at 80–120 ꢀC in the absence of acid catalyst. Our inves-
tigation demonstrated that the best result was obtained when temperature was fixed
at 110 ꢀC, in which the reaction was completed in 5 min. Therefore, we decided to
examine the other reactions in solvent-free and catalyst-free conditions at 110 ꢀC.
Bis-Schiff bases (3a–l) were prepared by combining 1 equivalent of bis-amine 1
with 2 equivalents of aromatic aldehydes (2a–l) in solventless conditions during
2–5 min at 110 ꢀC (Scheme 1). These reactions require neither solvent nor inert
atmosphere conditions. Each compound was isolated by the addition of ethanol to
a cooled reaction mixture and filtration of the resulting precipitate in good to excel-
lent yields. The results of these reactions are shown in Table 1.
Scheme 1. Synthesis of symmetrical bis-Schiff bases of 5,50-methylenebis(2-aminothiazole).

SIMPLE SYNTHESIS OF BIS-SCHIFF BASES
2533
Table 1. Synthesis of bis-Schiff bases (3a–l) under solventless conditions
Time
(min)
Yield
(%)
Mp (ꢀC)
(lit.[ref.]
Entry
Aldehyde
Product
)
245–247
(244–246[19]
1
5
4
94
91
)
2
220–222
225–226
(222–224[19]
3
2
90
)
4
4
88
171–172
5
6
7
5
5
3
91
89
94
227–229
141–143
224–225
(Continued )

2534
A. SHOCKRAVI, M. SADEGHPOUR, AND A. OLYAEI
Table 1. Continued
Time
(min)
Yield
(%)
Mp (ꢀC)
(lit.[ref.]
Entry
Aldehyde
Product
)
259–261
(258–260[19]
8
3
95
92
)
268–269
(266–267[19]
9
2
3
)
194–196
(195–197[19]
10
88
)
182–183
(181–182[19]
11
12
2
3
85
92
)
260 (dec)
In all cases, aromatic aldehydes with substituents carrying either electron-
donating or electron-withdrawing groups reacted successfully and gave the products
in good yields. This method can be compared with our previous work, which has
occurred in solution.[20] It is concluded that the yields of Schiff base products in this
method were better and that the reaction times were lower. Also, these reactions
were carried out without a catalyst in solventless conditions.
The structure of new products has been assigned by spectroscopic data. In the
=
infrared (IR) spectra, the characteristic Schiff base C N stretching frequency is
1
absorbed in the region t ¼ 1585–1615 cmꢁ1 as a strong band. In the H NMR spec-
tra, methylene protons are absorbed in the region d ¼ 4.42–4.55 ppm, imine protons
in the region d ¼ 8.84–9.33 ppm, hydroxyl proton of compound 3b at the region
d ¼ 10.44 ppm, NH proton of the compound 3 l at d ¼ 12.34 ppm, and protons of
aromatic rings at around d ¼ 6.91–8.62 ppm. Mass spectra (MS) revealed the molecu-
lar ion peaks (M, M þ 2, and M þ 4) for compound 3d with intensities 1:2:1 are due

SIMPLE SYNTHESIS OF BIS-SCHIFF BASES
2535
to two bromine atoms in these structures, and other products exhibited the parent
ions with medium intensity.
In conclusion, we have successfully developed a quick, convenient, efficient,
and uncatalyzed method for the synthesis of bis-Schiff bases under solvent-free con-
ditions. The environmental advantages include omitting organic solvent, generality
and simplicity of procedure, shorter reaction time, simple workup, catalyst-free
conditions, and pure products in good to excellent yields.
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, and the 1H and 13C NMR spectra were obtained using a Brucker Avance
DRX 500 apparatus at 298 K. Chemical shifts (d) are reported in parts per million
and are referenced to the NMR solvent peak. Elemental analyses were carried out
by a CHN-O-Rapid Heraeus elemental analyzer (Wellesley, Mass.). Mass spectra
of the products were obtained with an HP (Agilent Technologies) 5937 mass selective
detector. Progress of the reactions was monitored by thin-layer chromatography
(TLC) using precoated sheets of silica gel (Merck 60 F254) on aluminium.
General Procedure: Synthesis of Bis-Schiff Bases 3a–I
A mixture of compound 1 (1 mmol) and an aromatic aldehyde (2 mmol) was
magnetically stirred on a preheated oil bath at 110 ꢀ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
(10 mL) was added. Then the mixture was cooled to 0–5 ꢀC. The precipitate was fil-
tered, washed with cold ethanol, dried, and purified by recrystallization from EtOH
to give bis-Schiff base 3 as colored crystals.
Selected Data
5,5’-Methylene-bis[4-(thiazol-2-ylimino)methyl)phenol] (3b). Yellow
crystals; IR (KBr): 3369 (OH), 1592 (C Nimine) cmꢁ1
1H NMR (500 MHz,
=
;
DMSO-d6): d ¼ 4.42 (s, 2H, CH2), 6.91 (d, 4H, J ¼ 8.0 Hz, phenyl-H), 7.54 (s, 2H,
thiazol-H), 7.85 (d, 4H, J ¼ 8.0 Hz, phenyl-H), 8.84 (s, 2H, imine-H), 10.44 (s, 2H,
OH) ppm; 13C NMR (125 MHz, DMSO-d6): d ¼ 25.74, 116.89, 126.92, 132.90,
136.24, 136.85, 139.67, 164.12, 172.88 ppm; MS: m=z ¼ 420 [M]þ, 405, 377, 262,
236, 212, 183, 152, 121, 97. Anal. calcd. for C21H16N4O2S2: C, 60.00; H, 3.81, N,
13.33. Found: C, 60.10; H, 3.70, N, 13.38.
5,5’-Methylene-bis[N-(3-bromobenzylidene)-2-aminothiazol] (3d). Yellow
=
crystals; IR (KBr): 1615 (C Nimine) cmꢁ1; 1H NMR (500 MHz, DMSO-d6): d ¼ 4.52
(s, 2H, CH2), 7.49–8.17 (m, 8H, phenyl-H), 7.66 (s, 2H, thiazol-H), 9.01 (s, 2H,
imine-H) ppm; 13C NMR (125 MHz, DMSO-d6): d ¼ 25.64, 123.16, 129.30, 132.10,
132.66, 136.16, 137.88, 137.97, 140.32, 159.80, 163.34 ppm; MS: m=z ¼ 544 [M]þ,

2536
A. SHOCKRAVI, M. SADEGHPOUR, AND A. OLYAEI
546 [M þ 2]þ, 548 [M þ 4]þ, 379, 320, 226, 212, 196, 169, 152, 128. Anal. calcd. for
C21H14Br2N4S2: C, 46.15; H, 2.56; N, 10.25. Found: C, 46.18; H, 2.48; N, 10.36.
5,5’-Methylene-bis[N-(4-chlorobenzylidene)-2-aminothiazol] (3e). Yellow
=
crystals; IR (KBr): 1601 (C Nimine) cmꢁ1; 1H NMR (500 MHz, DMSO-d6): d ¼ 4.51
(s, 2H, CH2), 7.63 (d, 4H, J ¼ 8.5 Hz, phenyl-H), 7.64 (s, 2H, thiazol-H), 8.03 (d, 4H,
J ¼ 8.5 Hz, phenyl-H), 9.03 (s, 2H, imine-H) ppm; 13C NMR (125 MHz, DMSO-d6):
d ¼ 25.52, 114.55, 130.12, 132.06, 134.28, 137.70, 140.22, 163.62, 171.81 ppm; MS:
m=z ¼ 457 [M]þ, 334, 318, 274, 235, 182, 165, 150, 128. Anal. calcd. for
C21H14Cl2N4S2: C, 55.14; H, 3.03; N, 12.25. Found: C, 55.19; H, 2.95; N, 12.34.
5,5’-Methylene-bis[N-(2-chlorobenzylidene)-2-aminothiazol] (3f). Yellow
crystals; IR (KBr): 1585 (C Nimine) cmꢁ1
1H NMR (500 MHz, DMSO-d6):
=
;
d ¼ 4.53 (s, 2H, CH2), 7.49–8.19 (m, 8H, phenyl-H), 7.68 (s, 2H, thiazol-H), 9.33
(s, 2H, imine-H) ppm; 13C NMR (125 MHz, DMSO-d6): d ¼ 25.58, 128.79, 129.61,
131.25, 132.30, 135.18, 136.95, 138.42, 140.51, 159.67, 171.61 ppm; MS: m=z ¼ 457
[M]þ, 421, 352, 334, 318, 299, 284, 274, 224, 200, 182, 165, 150, 128. Anal. calcd.
for C21H14Cl2N4S2: C, 55.14; H, 3.03; N, 12.25. Found: C, 55.05; H, 2.98; N, 12.16.
5,5’-Methylene-bis[N-(4-chloro-3-nitrobenzylidene)-2-aminothiazol] (3g).
1
Yellow crystals; IR (KBr): 1598 (C Nimine) cmꢁ1; H NMR (500 MHz, DMSO-d6):
=
d ¼ 4.55 (s, 2H, CH2), 7.70 (s, 2H, thiazol-H), 7.95–8.62 (m, 6H, phenyl-H), 9.13 (s,
2H, imine-H) ppm; 13C NMR (125 MHz, DMSO-d6): d ¼ 24.69, 125.82, 128.60,
132.51, 133.73, 134.98, 137.63, 139.65, 147.89, 160.88, 170.11 ppm; MS: m=z ¼ 547
[M]þ, 529, 379, 362, 319, 273, 227, 184, 152, 128. Anal. calcd. for C21H12Cl2N6O4S2:
C, 46.06; H, 2.19; N, 15.36. Found: C, 46.00; H, 2.10; N, 15.48.
5,5’-Methylene-bis[N-(1H-3-indolyl methylene)-2-aminothiazol] (3l).
Orange crystals; IR (KBr): 3200 (NH), 1598 (C Nimine) cmꢁ1
;
1H NMR
=
(500 MHz, DMSO-d6): d ¼ 4.40 (s, 2H, CH2), 7.22–7.28, 7.52–8.30 (m, 10H,
indol-H), 7.48 (s, 2H, thiazol-H), 9.07 (s, 2H, imine-H), 12.34 (s, 2H, NH) ppm;
13C NMR (125 MHz, DMSO-d6): d ¼ 25.92, 113.32, 115.04, 122.58, 122.74, 124.25,
125.41, 134.80, 138.09, 138.35, 139.22, 159.33, 174.55 ppm; MS: m=z ¼ 466 [M]þ,
421, 368, 339, 313, 299, 285, 264, 236, 212, 152, 128. Anal. calcd. for C25H18N6S2:
C, 64.37; H, 3.86; N, 18.02. Found: C, 64.25; H, 3.89; N, 18.10.
ACKNOWLEDGMENT
We thank the Research Council of the Tarbiat Moallem University for
financial support.
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