Synthesis and spectroscopic studies of new schiff bases

Article abstract of DOI:10.3390/11020206

Five novel Schiff bases have been prepared from o-formylphenoxyacetic acid and a series of aminothiazoles to form a number of potentially biologically active compounds. The structures of these Schiff bases have been characterized using IR and ¹

Full text of DOI:10.3390/11020206

Molecules 2006, 11, 206-211
molecules
ISSN 1420-3049
http://www.mdpi.org
Short Communication
Synthesis and Spectroscopic Studies of New Schiff Bases
1
,
1
3
2,*
Hamid Latif Siddiqui * Amjid Iqbal , Saeed Ahmad and George W. Weaver
1
Institute of Chemistry, University of the Punjab, Lahore-5400, Pakistan
2
Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK
Pakistan Council of Science and Industrial Research Complex, Lahore, Pakistan
3
*
Authors to whom correspondence should be addressed: E-mail: drhamidlatif@yahoo.com;
G.W.Weaver@lboro.ac.uk
Received: 2 August 2005; revised version received: 10 March 2006 / Accepted: 10 March 2006 /
Published: 17 March 2006
Abstract: Five novel Schiff bases have been prepared from o-formylphenoxyacetic acid
and a series of aminothiazoles to form a number of potentially biologically active
1
compounds. The structures of these Schiff bases have been characterized using IR and H-
1
3
and C-NMR spectroscopy.
Keywords: aminothiazoles, o-formylphenoxyacetic acid, Schiff bases, biological activity
Introduction
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 have biological activities such as antimicrobial [2-5], antifungal [4-6],
antitumor [7-9], and as herbicides [10]. Schiff bases have also been employed as ligands for
complexation of metal ions [11]. On the industrial scale, they have wide range of applications such as
dyes and pigments [12]. Keeping in view the facts mentioned, we decided to synthesize new Schiff
bases which were predicted to have useful biological activity. The synthesis of other similar Schiff
bases, their biological activity, and complex formation are under study.

Molecules 2006, 11
207
Results and Discussion
The Schiff bases 2a-e were synthesized by condensation of o-formylphenoxyacetic acid and aryl
aminothiazoles 1a-e by reaction in hot ethanol or dioxane using sodium sulfate as a dehydrating agent.
The aminothiazoles were prepared by the known [13] reaction of thiourea with substituted
acetophenones in the presence of iodine as oxidant. Good yields were obtained for the Schiff bases,
although in some cases the addition of ytterbium triflate was found to improve the yield of product, it
acting as a Lewis acid catalyst.
R2
R2
R3
R3
1
2
3
a R = Br, R = H, R = H
R1
N
R1
N
1
2
3
b R = H, R = H, R = Br
1
2
3
c R = F, R = H, R = H
O
CO H
2
1
2
3
d R = H, R = F, R = H
1
2
3
N
e R = H, R = H, R = F
NH2
S
S
1
a-e
2a-e
Acknowledgements
We greatly acknowledge the Higher Education Commission of Pakistan, Islamabad, as well as
University of the Punjab, Lahore and Loughborough University for financial support. We thank Mr
John C. Kershaw for running mass spectra and Mr J. Alastair Daley for elemental analysis.
Experimental
General
Bromoacetophenones, chloroacetophenones and fluoroacetophenones were obtained commercially
from Lancaster Research Chemicals and 2-formylphenoxyactic acid from the Aldrich Chemical
1
13
Company. H-NMR and C-NMR spectra were recorded on a Bruker DPX-400 instrument at 400 and
00 MHz, respectively. Chemical shifts are reported in ppm referenced to the residual solvent signal.
1
IR spectra were recorded on a Perkin Elmer Paragon 1000 spectrometer. Mass spectra were recorded
on a Jeol SX-102 instrument using FAB ionization. Melting points were recorded on a Stuart
Scientific-SMP3 apparatus and are uncorrected.
Synthesis of 2-amino-4-(2’-bromophenyl)-thiazole (1a)
Method A: The title compound was prepared by addition of resublimed iodine (2.54 g, 0.01 mol) to
2
’-bromoacetophenone (1.99 g, 0.01 mol) and thiourea (1.52 g, 0.02 mol), followed by heating of the
mixture overnight in an oil bath at 100 °C. After cooling, the reaction mixture was triturated with
diethyl ether (ca. 50 mL) to remove any unreacted iodine and bromoacetophenone. The solid residue
was put in cold distilled water (200 mL) and treated with 25% aqueous ammonium hydroxide (to pH
9
-10). The precipitated thiazole was collected and purified by crystallization from hot ethanol. The
+
yield was 85% and m.p. 123 °C; FABMS: m/z 255 (MH ) , in agreement with the molecular formula

Molecules 2006, 11
BrN S; IR; IR (υmax, KBr, cm ): 3320 (d of NH
208
-
1
C
9
H
7
2
1
2
); 1510, 1460, 1045 (characteristic of the thiazole
4
nucleus); H-NMR (MeOH-d ): δ 6.87 (1H, s, thiazole H-5), 7.34 (1H, td, J 11.6, 1.6 Hz, ArH), 7.45
1
3
(
1H, td. J 7.6,1.6 Hz, ArH), 7.58 (1H, dd, J 7.2, 1.2 Hz, ArH), 7.72 (1H, dd, J 8.0,1.2 Hz, ArH); C-
4
NMR (MeOH-d ): δ 171.2, 144.6, 134.9, 133.1, 131.7, 130.0, 128.8, 123.4, 107.7; Anal. Calcd. for
9 7 2
C H BrN S: C, 42.37; H, 2.77; N, 10.98; Found: C, 42.39; H, 2.76; N, 10.96.
Method B: 2-Amino-4-(2’-bromophenyl)-thiazole was also prepared following the reported procedure
14]. The spectroscopic data of the compound 1a thus prepared were identical to those given above.
[
The following compounds were prepared by Method A, as described above:
2-amino-4-(4’-bromophenyl)thiazole (1b)
+
Yield: 80%; m.p. 178 ºC; FABMS: m/z 255 (MH ), in agreement with the molecular formula
-
1
C
9
H
7
BrN
2
1
S; IR (υmax, KBr, cm ): 3320 (d of NH
2
); 1515, 1455, 1050 (characteristic of the thiazole
): δ 8.7-7.8 (2H, bs, NH ), 7.67 (4H, s, ArH), 7.07 (1H, s, thiazole H-5);
): δ 169.7, 140.7, 131.8, 129.5, 127.8, 122.0, 103.5; Anal. Calcd. for C BrN S:
C, 42.37; H, 2.77; N, 10.98; Found: C, 42.35; H, 2.75; N, 10.97.
nucleus); H-NMR (DMSO-d
6
2
1
3
C-NMR (DMSO-d
6
9
H
7
2
2-amino-4-(2’-fluorophenyl)thiazole (1c)
+
Yield: 97%; FABMS: m/z 195 (MH ), in agreement with the molecular formula C
9
H
7
FN
2
S; IR
-
1
1
(
υ
max, KBr, cm ): 3320 (d of NH
2
); 1510, 1455, 1050 (characteristic of the thiazole nucleus); H-NMR
(
MeOH-d
4
): δ 6.93 (1H, s, thiazole H-5), 7.13-7.36 (3H, m, ArH), 7.93 (1H, td, J 7.9, 1.7 Hz, ArH);
): δ 170.7, 145.1, 133.5, 133.4, 132.4, 131.4, 130.8, 128.2 and 107.9. Anal. Calcd.
S: C, 55.66; H, 3.63; N, 14.42; Found: C, 55.62; H, 3.59; N, 14.41.
1
3
C-NMR (MeOH-d
FN
4
for C
9
H
7
2
2-amino-4-(3’-fluorophenyl)thiazole (1d)
+
Yield: 86%; FABMS: m/z 194 (MH ), in agreement with the molecular formula C
9
H
7
FN
2
S; IR
-
1
1
(
(
υ
max, KBr, cm ): 3320 (d of NH
MeOH-d ): δ 7.01 (s, thiazole H-5), 7.09-7.56 (4H, m, ArH); C-NMR (MeOH-d
63.3, 135.9, 131.7, 122.8, 116.2, 113.8 and 104.5. Anal. Calcd. for C FN S: C,55.66; H, 3.63, N,
2
); 1510, 1460, 1045 (characteristic of the thiazole nucleus); H-NMR
1
3
4
4
): δ 171.8, 165.7,
1
1
9
H
7
2
4.42; Found: C, 55.60; H, 3.58, N, 14.39.
2-amino-4-(4’-fluorophenyl)thiazole (1e)
+
Yield: 87%; FABMS: m/z 195 (MH ), in agreement with the molecular formula C
9
H
7
FN
2
S; IR
-
1
1
(
(
υ
max, KBr, cm ): 3320 (d of NH
Py-d ): δ 7.31 (2H, brs, NH
71.4, 165.2, 162.7, 133.9, 129.9, 129.8, 117.3, 117.1 and 103.5; Anal. Calcd. for C
5.66; H, 3.63; N, 14.42; Found: C, 55.65; H, 3.61; N, 14.40.
2
); 1510, 1460,1045 (characteristic of the thiazole nucleus); H-NMR
1
3
5
2
), 8.10 (1H, s, thiazole H-5), 8.18-9.20 (4H, m, ArH); C (Py-d
5
): δ
1
5
9 7 2
H N
FS: C,

Molecules 2006, 11
209
Preparation of (2-{[4-(2-bromophenyl)thiazol-2-ylimino]methyl}phenoxy)acetic acid (2a):
2
-Formylphenoxyacetic acid (4.0 mmol, 0.72 g) was added to 2-amino-4-(2’-bromophenyl)-
thiazole (4.0 mmol, 1.02 g) in absolute EtOH (20 mL) in addition to molecular sieves (4Å, ca. 5 g) and
Na SO (anhydr. ca. 5 g) and refluxed (oil bath at 90 ºC) for 3 days under N (g). After filtration,
2
4
2
evaporation and recrystallisation from EtOH the yield of the title Schiff base was found to be 60%;
+
m.p. 180 ºC; HRMS (FAB, MH ) calcd. for C18
H
13
N
2
O
3
BrS: 416.9909, found: 416.9904; IR (υmax
): δ 5.77 (2H, s, CH ), 6.91 (1H, d, J
): δ 67.1, 113.4,
22.1, 122.3, 128.4, 129.5, 130.0, 130.8, 131.1, 130.3, 133.2, 133.8, 136.4, 144.9, 156.3, 1661.5,168.9,
72.0; Anal. Calcd. for C18 S: C, 51.81; H, 3.14; N, 6.71. Found: C, 51.79, H, 3.12; N, 6.69;
,
-
1
-1 1
KBr, cm ): 3030, 1635, 1550, 1240 cm ; H-NMR, (MeOH-d
4
1
2
3
9
1
1
.2 Hz, ArH), 7.46-7.73 (7H, m, ArH), 7.92 (1H, s CH=N); C-NMR (MeOH-d
4
H
2 3
13BrN O
Preparation of (2-{[4-(4-bromophenyl)-thiazole-2-ylimino]methyl}phenoxy)acetic acid (2b)
2
-Formylphenoxyacetic acid (4.0 mmol, 0.72 g) was added to a solution of 2-amino-4-(4’-
bromophenyl)-thiazole (4.0 mmol, 1.02 g) in dioxane (40 mL) in addition to molecular sieves (4Å, ca.
g) and Na SO (anhydr. ca. 5 g) and refluxed above 100 ºC for 2 days under N (g). The product was
5
2
4
2
purified by crystallization from EtOH and the yield of the Schiff base was found to be 67%; m.p. 185-
+
1
87 ºC; HRMS (FAB, MH ) calcd. for C18
H
13BrO
3
N
2
S: 416.9909, found: 416.9904; IR (υmax, KBr,
S: C, 51.81; H, 3.14; N, 6.71. Found: C,
), 6.77 (1H, d, J 8.0 Hz, ArH) 7.10-
): δ 65.9,113.4, 122.8, 122.9, 123.9,
24.4, 129.4, 129.8, 130.7, 131.0, 131.1, 131.2, 132.8, 132.9, 140.1, 156.3, 160.9, 172.0
-
1
cm ): 3030, 1650, 1550, 1240. Anal. Calcd. for C18
H
13BrO
3
N
2
1
5
7
1
1.80, H, 3.10; N, 6.70; H-NMR, (MeOH-d
4
3
): δ 6.17 (2H, s, CH
2
1
.63 (7H, m, ArH), 7.99 (1H, s, CH=N); C-NMR (MeOH-d
4
Preparation of (2-{[4-(2’-fluorophenyl)-thiazole-2-ylimino]methyl}phenoxy)acetic acid (2c)
2-Formylphenoxyacetic acid (1.0 mmol, 0.18 g) was added to a solution of 2-amino-4-(2’-
fluorophenyl)-thiazole (1.0 mmol, 0.19 g) in absolute EtOH (10 mL) in addition to 10% mmol of
Yb(OTf)
3
as Lewis catalyst and refluxed for 10 hours under N
2
(g). The reaction mixture was filtered
®
through a column of silica gel, charcoal and Celite to remove the catalyst. After evaporation of the
ethanol, the product was purified by recrystallisation from CHCl
3
/MeOH (a few drops) to give the
S: 357.0709,
): δ 5.64 (2H, s,
): δ 66.3, 116.8, 122.2,
22.5, 125.1, 126.3, 128.1, 128.4, 129.3, 130.3, 130.9, 132.9, 138.2, 140.1, 157.2, 160.1, 169.5, 172.8;
Anal. calcd. for C18 S: C, 51.81; H, 3.14; N, 6.71. Found: C, 51.60, H, 3.08; N, 6.64;
+
Schiff base in 70% yield; m.p. 167 ºC; HRMS (FAB, MH ) calcd. for C18
H
13FN
2
O
3
-
1
1
found: 357.0712; IR (υmax, KBr, cm ): 3030, 1640, 1550, 1240; H-NMR, (MeOH-d
4
13
2 4
CH ), 6.79-7.68 (8H, m, ArH), 7.99 (1H, s, CH=N); C-NMR (MeOH-d
1
H
2 3
13FN O
Preparation of (2-{[4-(3’-fluorophenyl)thiazole-2-ylimino]methyl}phenoxy)acetic acid (2d)
Compound 2d was synthesized by the method described above. The product was purified by
crystallization from chloroform and the yield of the title Schiff base was 70%; m.p. 178 ºC (decomp.);
+
-1
HRMS (FAB, MH ) calcd. for C18
H
13FN
2
O
3
S: 357.0709; found: 357.0712; IR (υmax, KBr, cm ): 3030,
1
1
635, 1550, 1240; H-NMR (MeOH-d
4
): δ 6.15 (2H, s, CH ), 6.93-7.37 (8H, m, ArH), 7.91 (1H, s,
2

Molecules 2006, 11
210
1
3
CH=N); C-NMR (MeOH-d
4
): δ 66.3, 113.4, 116.4, 122.3, 124.6, 124.9, 125.3, 129.4, 130.4, 131.2,
1
31.3, 131.5, 131.6, 138.9, 140.9, 157.9, 162.4, 169.7; Anal. Calcd. for C18
.14; N, 6.71. Found: C, 51.64, H, 3.10; N, 6.56.
2 3
H13FN O S: C, 51.81; H,
3
Preparation of (2-{[4-(4’-fluorophenyl)-thiazole-2-ylimino]methyl}phenoxy)acetic acid (2e)
Compound 2e was synthesized by the method described above. The product was purified by
crystallization from chloroform and the yield of the Schiff base was 70%; m.p. 158-160 ºC; HRMS
+
-1
(
FAB, MH ) calcd. for C18
H
13FN
2
O
3
S: 357.0709, found: 357.0713; IR (υmax, KBr, cm ): 3030, 1630,
): δ 6.09 (2H, s, CH ), 6.90-7.48 (8H, m, ArH), 7.91 (1H, s, CH=N);
4
): δ 66.0,113.4, 116.6, 116.8, 122.9, 123.6, 128.0, 129.4, 130.5, 131.0, 131.7,
1
1
1
550, 1240; H-NMR (MeOH-d
4
2
3
C-NMR (MeOH-d
1
31.8, 138.9, 140.6, 156.4,163.2, 165.7, 171.6; Anal. Calcd. for C18
.71. Found: C, 51.59, H, 3.40; N, 6.49;
2 3
H13FN O S: C, 51.81; H, 3.14; N,
6
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