Synthesis of novel symmetrical bis-Schiff bases of 5,5′- methylenebis(2-aminothiazole)

Article abstract of DOI:10.1002/jhet.5570450536

(Chemical Equation Presented) Novel symmetrical bis-Schiff bases have been prepared cleanly and efficiently in the presence of formic acid catalyst in methanol from the reaction of symmetrical primary bis-amine of 5,5′-methylenebis(2-aminothiazole) (1) and a series of aromatic aldehyde derivatives under mild conditions. The advantages of this reaction are simplicity of the reaction procedure, simple work-up and pure products with high yields. The structures of all the new synthesized symmetrical bis-Schiff bases were confirmed by elemental analyses, IR, ¹H-NMR, ¹³C-NMR and mass spectra.

Full text of DOI:10.1002/jhet.5570450536

Sep-Oct 2008
1473
Synthesis of Novel Symmetrical bis-Schiff Bases of
5,5'-Methylenebis(2-aminothiazole)
Abbas Shockravi,a,* Abolfazl Olyaei,b Mahdieh Sadeghpoura
aFaculty of Chemistry, Tarbiat Moallem University, Mofatteh Ave., No 49, Postal Code 15614, Tehran, Iran
bDepartment of Chemistry, Payame Noor University, Qazvin, Iran
Tel.: 0098-21-8832920; Fax: 0098-21-88825580; E-mail: Shockravi@tmu.ac.ir Abbas_shockravi@yahoo.co.uk
Received September 4, 2007
N
N
N
S
S
N
HCOOH
S
S
+ ArCHO
N
N
MeOH
r.t.
NH2
H2N
Ar
Ar
1
2
3
Ar= a: 2-OH-C6H4; b: 2-OH-5-Br-C6H3; c: 2-OH-5-NO2-C6H3; d: 4-Br-C6H4; e: 3-NO2-C6H4; f: 2-C4H3S
Novel symmetrical bis-Schiff bases have been prepared cleanly and efficiently in the presence of formic
acid catalyst in methanol from the reaction of symmetrical primary bis-amine of 5,5'-methylenebis(2-
aminothiazole) (1) and a series of aromatic aldehyde derivatives under mild conditions. The advantages of
this reaction are simplicity of the reaction procedure, simple work-up and pure products with high yields.
The structures of all the new synthesized symmetrical bis-Schiff bases were confirmed by elemental
analyses, IR, 1H-NMR, 13C-NMR and mass spectra.
J. Heterocyclic Chem., 45, 1473 (2008).
INTRODUCTION
catalyst in methanol under mild conditions. The
complexing studies of Schiff base derivatives of this
ligand with heavy metal ions are under study in our
research laboratory.
Condensation of carbonyl compounds with primary
amines was discovered in 1864 by Hugo Schiff [1]. This
acid-catalyst reaction is universal and makes it possible to
obtain a broad variety of azomethines. Schiff bases
ligands, as variety of compounds with imine group have
gained importance because of biological activities such as
antimicrobial [2-5], antifungal [6], antitumor [7] and
pharmacological activities associated with them. On the
industrial scale, they have wide range of applications such
as dyes and pigments [8]. They constitute an interesting
class of chelating agents capable of metal complexation,
which serves as models for biological system [9-11].
Conventionally Schiff bases have been prepared by
refluxing mixtures of the amine and carbonyl compounds
in an organic solvent (ethanol or methanol) [12]. Also the
other reaction conditions were investigated for the
synthesis of Schiff bases in the literature. For example,
treatment of the above mixture has been studied at room
temperature, refluxing in heptane as solvent in the
presence of acetic acid as catalyst [13], or forming an
azeotropic mixture of benzene and water in the presence
of acid and using a Dean-Stark [14] apparatus to remove
the water. Based on investigations in literature, it appears
that the reaction of carbonyl compounds with bis-amine
of 5,5'-methylenebis(2-aminothiazole) (1) [15] for the
synthesis of symmetrical diimino Schiff bases have not
been studied before.
RESULTS AND DISCUSSION
The bis-Schiff bases 3a-f were synthesized by
condensation of 5,5'-methylenebis(2-aminothiazole) (1) and
aromatic aldehydes 2a-f (2-hydroxy benzaldehyde,
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 (Scheme 1).
In the IR spectra of 3a-f the characteristic C=N
absorption bands appeared at 1626, 1594, 1610, 1631,
1599 and 1596 cm-1, respectively. Hydroxyl absorption
bands for 3a-c were not absorbed in the IR spectra
because the hydroxyl groups located at the ortho position
with respect to the imino groups were involved enol-keto
tautomerisation process when ortho and para hydroxyl
derivatives of aromatic aldehydes were used. Hydroxyl
protons of 3a-c in 1H NMR spectrum observed broad
signals at ꢀ 11.51, 11.52 and 10.28 ppm due to enol-keto
tautomerisation, imine moiety appeared as a singlet signal
in 3a-f at about ꢀ 9.1 ppm and remaining protons of the
corresponding aromatic molecules showed in the aromatic
regions. Mass spectra revealed the molecular ion peaks
(M, M+2 and M+4) for compounds 3b and 3d with
intensities 1:2:1 due to have two bromine atoms in these
structures and other products exhibited the parent ions
with medium intensity.
In the present paper, we report the synthesis of novel
symmetrical bis-Schiff bases of diamine 1 and aromatic
aldehyde derivatives 2 in the presence of formic acid

1474
A. Shockravi, A. Olyaei, M. Sadeghpour
Vol 45
Table 1
Yields, melting points and reaction times of compounds 3a-f
Scheme 1
N
N
S
S
+ ArCHO
Entry
Ar
Time
hours
Mp
Yield
%
Color
NH2
H2N
(°C)
1
2
244-
246
HCOOH
MeOH
3a
16
85
Yellowish
r.t.
HO
Br
N
N
265-
267
3b
3c
20
83
Yellow
Orange
S
S
N
N
HO
NO2
Ar
Ar
3
258-
260
12
90
NO2
Br
HO
Ar = a:
c:
b:
222-
224
Br
3d
3e
25
21
79
80
Yellow
Yellow
HO
HO
HO
195-
197
Br
d:
e:
f:
NO2
S
NO2
179-
181
3f
25
78
Yellow
S
The ion fragmentation of compounds 3a-f is almost
similar to each other. For example, ion fragmentation of
compound 3e is depicted in Scheme 2 as the
representative common features of the parent ion
decomposition.
All of the obtained products 3a-f were colored powders
and pure without purification. Yields, melting points and
reaction times are presented in Table 1.
Scheme 2
N
N
S
S
N
N
3e
NO2
O2N
m/z 478
N
N
S
S
N
N
NH2
S
N
H
N
N
N
N
N
S
S
S
NO2
H2N
NH2
H2N
m/z 212
-NH2CN
m/z 152
m/z 285
m/z 345
NO2
N
-NH2CN
S
S
N
S
S
S
H2N
H2N
m/z 128
m/z 170
m/z 113

Sep-Oct 2008
Synthesis of Novel Symmetrical bis-Schiff Bases
1475
ppm (broad, 2H, OH); 13C nmr (DMSO-d6): ꢀ 24.63, 117.77,
120.19, 125.29, 129.20, 137.26, 139.53, 139.89, 159.53, 164.90,
169.83; ms: m/z 510 (M+), 493, 361, 344, 212, 192, 152, 128,
113; Anal. Calcd. For C21H14N6O6S2: C, 49.41; H, 2.74; N,
16.47. Found: C, 49.35; H, 2.67; N, 16.37.
In summery, the reaction between bis-amine 1 with
aromatic aldehydes 2a-f in methanol under mild
conditions provides a series of novel symmetrical bis-
Schiff bases 3a-f. In this method, undesired products with
low yields were very soluble in methanol and colored
pure powders of desired products with high yields were
obtained. The compounds 3a-f as potential chelating
agents for metal coordination is under study in our
research laboratory.
5,5'-Methylenebis[N-(4-bromobenzylidene)-2-amino thiaz-
1
ol] (3d). ir (potassium bromide): 1631 (C=Nimine) cm-1; H nmr
(DMSO-d6): ꢀ 4.50 (s, 2H, CH2), 7.76 and 7.94 (dd, 8H, J = 8.52
Hz, Ar-H), 7.64 (s, 2H, thiazol-H), 9.01 ppm (s, 2H, imine-H);
13C nmr (DMSO-d6): ꢀ 24.69, 126.56, 127.88, 131.22, 132.09,
133.80, 136.76, 139.28, 162.81; ms: m/z 543 (M+), 545 (M+2),
547 (M+4), 381, 379, 377, 320, 318, 281, 279, 212, 200, 183,
170, 152, 128,113; Anal. Calcd. For C21H14 Br2N4 S2: C, 46.15;
H, 2.56; N, 10.25. Found: C, 46.10; H, 2.47; N, 10.29.
EXPERIMENTAL
5,5'-Methylenebis[N-(3-nitrobenzylidene)-2-amino thiazol]
(3e). ir (potassium bromide): 1599 (C=Nimine) cm-1; 1H nmr
(DMSO-d6): ꢀ 4.54 (s, 2H, CH2), 7.69 (s, 2H, thiazol-H), 7.82-
8.78 (m, 8H, Ar-H), 9.18 ppm (s, 2H, imine-H); 13C nmr
(DMSO-d6): ꢀ 24.54, 123.67, 126.80, 130.71, 135.25, 136.28,
137.45, 139.61, 148.26, 156.25, 162.07; ms: m/z 478 (M+), 345,
285, 212, 170, 152, 128, 113; Anal. Calcd. For C21H14N6O4S2: C,
52.72; H, 2.92; N, 17.57. Found: C, 52.65; H, 2.90; N, 17.50.
5,5'-Methylenebis[N-((thiophen-2-yl)methylene)-2-amino
thiazol] (4f). ir (potassium bromide): 1596 (C=Nimine) cm-1; 1H
nmr (DMSO-d6): ꢀ 4.44 (s, 2H, CH2), 7.26, 7.87 and 7.96 (m,
6H, Ar-H), 7.56 (s, 2H, thiazol-H), 9.14 ppm (s, 2H, imine-H);
13C nmr (DMSO-d6): ꢀ 24.76, 128.92, 133.97, 136.13, 136.94,
139.10, 140.83, 156.69, 170.90; ms: m/z 400 (M+), 334, 290,
246,231, 212, 154, 137, 128; Anal. Calcd. For C17H12N4S4: C,
51.00; H, 3.00; N, 14.00. Found: C, 50.98; H, 2.91; N, 14.09.
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 (ꢀ) are reported in ppm and are referenced to the NMR
solvent peak. Elemental analyses were carried out by a CHN-O-
Rapid Heraeus elemental analyzer (Wellesley, MA). Mass
spectra of the products were obtained with a HP (Agilent
technologies) 5937 Mass Selective Detector. Progress of the
reactions was monitored by TLC using precoated sheets of silica
gel Merck 60 F254 on aluminium.
General procedure for the synthesis of compounds 3a-f. A
solution of 5,5'-methylenebis(2-aminothiazole) (1.0 mmole),
aldehydes 2a-f (2.0 mmole), and formic acid (0.005 g of 98%
aqueous solution, 0.1 mmole), in methanol (40 mL) was stirred
at room temperature for the appropriate time (see Table 1).
Water was then added to the colored solutions of 3d, 3e until a
solid precipitated product was separated whereas in the reactions
of 3a, 3b, 3c and 3f the solid products were precipitated without
water addition. The precipitates were filtered, washed with cold
MeOH and dried.
Acknowledgement. We thank the Research Council of the
Tarbiat Moallem University for financial support.
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5,5'-Methylenebis[2-(thiazol-2-ylimino)methyl)phenol] (3a).
ir (potassium bromide): 1626 (C=Nimine) cm-1; 1H nmr (DMSO-
d6): ꢀ 4.48 (s, 2H, CH2), 6.96, 7.45 and 7.81 (m, 8H, Ar-H), 7.61
(s, 2H, thiazol-H), 9.22 (s, 2H, imine-H), 11.50 ppm (s, 2H,
OH); 13C nmr (DMSO-d6): ꢀ 24.45, 116.78, 119.49, 119.73,
131.17, 134.88 135.25, 136.47, 139.21, 160.10, 163.14; ms: m/z
420 (M+), 403, 316, 274, 241, 212, 159, 147, 132, 104; Anal.
Calcd. For C21H16N4O2S2: C, 60.00; H, 3.80; N, 13.33. Found: C,
59.91; H, 3.70; N, 13.36.
5,5'-Methylenebis[5-bromo-2-(thiazol-2-ylimino)methyl)-
1
phenol] (3b). ir (potassium bromide): 1594 (C=Nimine) cm-1; H
nmr (DMSO-d6): ꢀ 4.51 (s, 2H, CH2), 6.97, 7.60 and 7.99 (m, 6H,
Ar-H), 7.64 (s, 2H, thiazol-H), 9.19 (s, 2H, imine-H), 11.52 ppm
(s, 2H, OH); 13C nmr (DMSO-d6): ꢀ 24.41, 122.21, 119.11,
121.63, 122.21, 131.87, 136.04, 136.70, 138.49, 158.91, 160.46,
160.75; ms: m/z 576 (M+), 578 (M+2), 580 (M+4), 563, 561, 559,
396, 394, 379, 377, 354, 352, 321, 319, 239, 237, 225, 223, 212,
197, 182, 169, 155, 128, 103; Anal. Calcd. For C21H14Br2N4O2S2:
C, 43.59; H, 2.42; N, 9.68. Found: C, 43.49; H, 2.50; N, 9.61.
5,5'-Methylenebis[5-nitro-2-(thiazol-2-ylimino)methyl)-
[14] Vazzana, I.; Terranova, E.; Mattioli, F.; Sparatore, F.
Arkivoc 2004, 364.
1
phenol] (3c). ir (potassium bromide): 1610 (C=Nimine) cm-1; H
nmr (DMSO-d6): ꢀ 4.51 (s, 2H, CH2), 7.14, 8.27 and 8.72 (m,
6H, Ar-H), 7.65 (s, 2H, thiazol-H), 9.28 (s, 2H, imine-H), 12.36
[15] Ghandi, M.; Olyaei, A. J. Heterocyclic Chem. 2007, 44,
323.