Regioselective synthesis of novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole and 2,2′-(1,3-phenylene)bis(3-substituted-2- imino-4-phenyl-3H-thiazole) derivatives as antibacterial agents

Article abstract of DOI:10.1016/j.molstruc.2013.02.003

Several novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole derivatives were synthesized by the reaction of allyl-thioureas and 2-bromoacetophenone. We also report the synthesis of bis-allyl-3H thiazoles using the reaction of various isothiocyanates

Full text of DOI:10.1016/j.molstruc.2013.02.003

Journal of Molecular Structure 1039 (2013) 113–118
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Regioselective synthesis of novel 3-allyl-2-(substituted imino)-
4-phenyl-3H-thiazole and 2,20-(1,3-phenylene)bis
(3-substituted-2-imino-4-phenyl-3H-thiazole) derivatives as antibacterial agents
a
b
Jafar Abbasi Shiran a, Asieh Yahyazadeh a, , Manouchehr Mamaghani , Mehdi Rassa
⇑
a Department of Chemistry, Faculty of Sciences, University of Guilan, P.O. Box 1914, Rasht, Iran
b Department of Biology, Faculty of Sciences, University of Guilan, P.O. Box 41335-1914, Rasht, Iran
h i g h l i g h t s
"
"
"
Synthesis of allyl-1,3-thiazoline and bis(1,3-thiazoline) have been studies.
Antibacterial activity of 3H-thiazole and bis(3H-thiazole) derivatives were measured.
Bis-structure indicated higher antibacterial activity compare to other compounds.
a r t i c l e i n f o
a b s t r a c t
Article history:
Several novel 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole derivatives were synthesized by the
reaction of allyl-thioureas and 2-bromoacetophenone. We also report the synthesis of bis-allyl-3H thia-
zoles using the reaction of various isothiocyanates and 1,3-phenylenediamine. The structures of all com-
pounds were characterized by spectral and elemental analysis. Most of the synthesized compounds
exhibited efficient antibacterial activities against Salmonella enterica, Micrococcus luteus, Bacillus subtilis
and Pseudomonas aeruginosa.
Received 18 December 2012
Received in revised form 3 February 2013
Accepted 4 February 2013
Available online 14 February 2013
Keywords:
Allylisothiocyanate
Allylthiourea
Ó 2013 Elsevier B.V. All rights reserved.
Allyl-3H-thiazole
Bis-allyl-3H thiazole
Antibacterial activity
1. Introduction
3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole 2a-h (Scheme 1)
and 2,20-(1,3-phenylene)bis(3-substituted-2-imino-4-phenyl-3H-
Thiazoles and their derivatives exhibit various biological activ-
ities such as anti-bacterial [1], anti-fungal [2], anti-inflammatory
thiazole) 4a-c (Scheme 2) as antibacterial agents.
[3], anti-convulsant [4], pifithrin (pft-a), skin whitening agent
(KHG22394) [5], Furthermore, some thiazoles are used in agricul-
ture as pesticides and plant growth regulators [6]. Several novel
thiazole derivatives have been reported in literatures such as;
introduction of fluorine into thiazoline [7] and synthesis of sydno-
nyl substituted thiazolidinone and thiazoline derivatives [8]. The
above mentioned biological and synthetic significance of thiazole
derivatives promoted us to carry out the synthesis of some new
3-allyl-2- imino-4-phenyl-3H-thiazoles. We felt that introduction
of allyl groups into structure of 1,3-thiazolines can bring about sig-
nificant changes in the physicochemical and biological attributes.
Herein, we report a regioselective synthesis of new derivatives of
2. Experimental
2.1. Materials and methods
All commercially available chemicals and reagents were used
without further purification. Melting points were determined with
an Electrothermal model 9100 apparatus and are uncorrected. FT-
IR spectra were recorded on a Shimadzu 8400S spectrophotometer.
The NMR spectra were recorded on a Bruker AVANCE DMX400
spectrometer, operating at 400 MHz (1H NMR) and 100 MHz (13
C
NMR). The chemical shift values are expressed in ppm relative to
TMS as an internal standard. Elemental analyses were recorded
with a CHN model 2400 Perkin–Elmer and agreed with the calcu-
lated values.
⇑
Corresponding author. Tel./fax: +98 1313233262.
E-mail address: Yahyazadeh@guilan.ac.ir (A. Yahyazadeh).
0022-2860/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molstruc.2013.02.003

114
J. Abbasi Shiran et al. / Journal of Molecular Structure 1039 (2013) 113–118
Scheme 1. Synthesis of 3-allyl-2-(substituted imino)-4-phenyl-3H-thiazole.
Scheme 2. Synthesis of 2,20-(1,3)-phenylene) bis (3-substituted-2-imino-4-phenyl-3H-thiazole).
2.2. General procedure for synthesis of 1-allyl-2-(substituted imino)-
4-phenyl-3H-thiazole
2.2.1. 3-Allyl-2-(30-methoxyphenylimino)-4-phenyl-3H-thiazole (2a)
Yield 72%; white solid; mp 145–146 °C; FT-IR (KBr) (mmax
/
cmꢀ1): 3108, 2997, 2939, 2835, 1612, 1593, 1576, 1490, 1288,
1157, 1055, 1016, 996, 783, 698. 1H NMR (CDCl3, 400 MHz): dH
(ppm) 3.84 (s, 3H), 5.18 (d, 1H, J = 17.2 Hz), 5.32 (d, 1H,
J = 10.4 Hz), 5.42 (d, 2H, J = 4.8 Hz), 5.85–5.95 (m, 1H), 6.66 (s,
1H), 6.91 (dd, 1H, J = 8.4, 2.4 Hz), 7.19 (dd, 1H, J = 7.8, 2.4 Hz),
7.31–7.40 (m, 4H), 7.52 (t, 2H, J = 7.2 Hz), 7.58 (dd, 1H, J = 8.4,
7.8 Hz); 13C NMR (CDCl3, 100 MHz): dc (ppm) 51.0, 55.7, 104.2,
109.6, 114.8, 115.4, 118.9, 127.8, 129.3, 129.4, 129.6, 130.7,
131.1, 138.8, 143.5, 160.8, 168 ppm; Anal. Calcd for C19H18N2OS
(322.41): C, 70.78; H, 5.62; N, 8.68. Found: C, 70.76; H, 5.65; N,
8.70%.
Allylisothiocyanate was added dropwise to a stirred ethanol
solution of appropriate amine. The reaction mixtures were heated
at 50–60 °C for about 4 h and further stirred at room temperature
for 24 h. The reaction mixture was filtered to give corresponding
thiourea, which was used directly without further purification.
To a solution of thiourea in absolute ethanol, 2-bromoacetophe-
none and two drops of Et3N as catalyst were added and the mixture
was refluxed for several hours, a precipitate was formed. The mix-
ture was filtered and washed with ethanol, then recrystallized
from ethanol–water (1:1) to give the target compounds.

J. Abbasi Shiran et al. / Journal of Molecular Structure 1039 (2013) 113–118
115
2.2.2. 3-Allyl-2-(40-methoxyphenylimino)-4-phenyl-3H-thiazole (2b)
Yield 76%; white solid; mp 145–146 °C; FT-IR (KBr) (mmax
8.84 (d, 1H, J = 7.2 Hz) ppm; 13C NMR (CDCl3, 100 MHz): dc: 18.4,
47.8, 97.1, 116.5, 120.3, 123.7, 127.2, 127.3, 128.3, 128.5, 129.4,
129.1, 130.6, 131.0, 137.5, 140.7, 151.9, 159.3 ppm; Anal. Calcd
for C19H18N2S (306.43): C, 74.47; H, 5.92; N, 9.14. Found: C,
74.26; H, 6.27; N, 9.07%.
/
cmꢀ1): 3110, 2995, 2939, 2836, 1610, 1592, 1571, 1490, 1361,
1281, 1057, 950, 781. 1H NMR (CDCl3, 400 MHz): dH: 3.83 (s, 3H),
4.45 (d, 2H, J = 3.6 Hz), 5.04 (d, 1H, J = 17.2 Hz), 5.17 (d, 1H,
J = 10.4 Hz), 5.78 (s, 1H), 5.89–5.97 (m, 1H), 6.92 (d, 2H,
J = 8.6 Hz), 7.03 (d, 2H, J = 8.6 Hz), 7.40–7.48 (m, 5H) ppm; 13C
NMR (CDCl3, 100 MHz): dc: 47.5, 55.4, 95.5, 114.6, 116.4, 122.4,
128.5, 128.9, 129.1, 131.7, 132.8, 140.4, 145.2, 155.0, 159.6 ppm;
Anal. Calcd for C19H18N2OS (322.41): C, 70.78; H, 5.62; N, 8.68.
Found: 70.80; H, 5.59; N, 8.72%.
2.2.8. 3-Allyl-2-(p-hydroxyphenylimino)-4-phenyl-3H-thiazole (2h)
Yield 73%; white needles; mp 123–124 °C; FT-IR (KBr) (mmax
/
cmꢀ1): 3334, 2996, 2935, 1611, 1593, 1575, 1496, 1425, 1382,
1317, 1184, 1126, 991, 970, 840. 1H NMR (CDCl3, 400 MHz): dH:
4.73 (s, 2H), 4.97 (d, 1H, J = 17.2 Hz), 5.27 (d, 1H, J = 9.8 Hz),
5.84–5.91 (m, 1H), 6.96 (d, 2H, J = 8.4 Hz), 7.12 (s, 1H), 7.32 (d,
2H, J = 8.4 Hz), 7.53–7.58 (m, 5H), 9.98 (br, OH) ppm; Anal. Calcd
for C18H16N2OS (308.41): C, 70.10; H, 5.23; N, 9.08. Found: C,
70.01; H, 5.25; N, 9.16%.
2.2.3. 3-Allyl-2-(30,40-dimethoxyphenylimino)-4-phenyl-3H-thiazole
(2c)
Yield 64%; white solid; mp 145–146 °C; FT-IR (KBr) (mmax
/
cmꢀ1): 3096, 2976, 2926, 1614, 1560, 1458, 1238, 1058, 954,
900, 698, 605. 1H NMR (CDCl3, 400 MHz): dH: 3.88 (s, 6H), 4.44
(d, 2H, J = 4.4 Hz), 5.04 (d, 1H, J = 17.2 Hz), 5.17 (d, 1H,
J = 10.4 Hz), 5.78 (s, 1H), 5.89–5.98 (m, 1H), 6.66 (d, 1H,
J = 8.8 Hz), 6.68 (s, 1H), 6.86 (d, 1H, J = 8.8 Hz), 7.38–7.46 (m, 5H)
ppm; 13C NMR (CDCl3, 100 MHz): dc: 50.1, 51.2, 57.2, 103.4,
116.5, 117.3, 122.4, 128.3, 128.7, 128.9, 130.3, 131.8, 136.7,
141.1, 145.6, 150.1, 155.6, 163.2 ppm; Anal. Calcd for C20H20N2O2S
(352.43): C, 68.16; H, 5.71; N, 7.94. Found: C, 68.19; H, 5.73; N,
7.97%.
2.3. General procedure for synthesis of Bis[3-allyl(alkyl)-2-(substituted
imino)-4-phenyl-3H-thiazole]
Isothiocyanate (2 mmol) was added dropwise to a stirred etha-
nol solution of (1 mmol) of 1,3-phenylenediamine. The reaction
mixtures were heated at 50–60 °C for about 30 min and the mix-
ture was kept at room temperature for 24 h. The reaction mixture
was filtered to give corresponding dithiourea, which was used di-
rectly without further purification. Target compounds were then
synthesized in a similar way from dithiourea (1 mmol) and 2-bro-
moacetophenone (2 mmol).
2.2.4. 3-Allyl-2-(40-ethoxyphenylimino)-4-phenyl-3H-thiazole (2d)
Yield 59%; white solid; mp 145–146 °C; FT-IR (KBr) (mmax
/
cmꢀ1): 2972, 2922, 1616, 1541, 1506, 1458, 1315, 1236, 1116,
1051, 954. 1H NMR (CDCl3, 400 MHz): dH: 1.44 (t, 3H, J = 6.8 Hz),
4.05 (q, 2H, J = 6.8 Hz), 4.45 (d, 2H, J = 4.4 Hz), 5.05 (d, 1H,
J = 17.2 Hz), 5.17 (d, 1H, J = 10.4 Hz), 5.78 (s, 1H), 5.89–5.98 (m,
1H), 6.91 (2H, d, J = 8.4 Hz), 7.02 (d, 2H, J = 8.4 Hz) 7.43–7.46 (m,
5H) ppm; Anal. Calcd for C20H20N2OS (336.44): C, 71.40; H, 5.99;
N, 8.32. Found: C, 71.37; H, 6.04; N, 8.29%.
2.3.1. 2,20-(1,3-Phenylene) bis (3-methyl-2-imino-4-phenyl-3H-
thiazole) (4a)
Yield 56%; yellow solid; mp 185–186 °C; FT-IR (KBr) (mmax
/
cmꢀ1): 3079, 2920, 1608, 1594, 1574, 1476, 1415, 1362, 1142,
1055, 979, 877, 701, 500. 1H NMR (CDCl3, 400 MHz): dH: 3.39 (s,
6H), 5.82 (s, 2H), 6.82 (dd, 2H, J = 8.2, 1.6 Hz), 6.92 (s, 1H), 7.35
(t, 1H, J = 8.2 Hz), 7.40–7.48 (m, 10 H) ppm; 13C NMR (CDCl3,
100 MHz): dc: 33.9, 95.6, 113.9, 116.8, 128.6, 128.7, 129.0, 130.4,
2.2.5. 3-Allyl-2-(p-ethylphenylimino)-4-phenyl-3H-thiazole (2e)
Yield 62%; white solid; mp 145–146 °C; FT-IR (KBr) (mmax
/
cmꢀ1): 3074, 2924, 2861, 1599, 1565, 1481, 1380, 1222, 1073,
918, 701, 533. 1H NMR (CDCl3, 400 MHz): dH: 1.17 (t, 3H,
J = 7.6 Hz), 2.57 (q, 2H, J = 7.6 Hz) 4.46 (d, 2H, J = 3.6 Hz), 5.05
(1H, d, J = 17.2 Hz), 5.17 (1H, d, J = 10.4 Hz), 5.76 (s, 1H), 5.90–
5.98 (m, 1H), 6.93 (2H, d, J = 8 Hz), 7.04 (2H, d, J = 8 Hz), 7.41–
7.49 (m, 5H) ppm; Anal. Calcd for C20H20N2S (320.45): C, 74.96;
H, 6.29; N, 8.74. Found: C, 75.04; H, 6.21; N, 8.79%.
131.7, 140.4, 153.0, 160.4 ppm; Anal. Calcd for
C26H22N4S2
(454.60): C, 68.69; H, 4.87; N, 12.32. Found: C, 68.60; H, 5.01; N,
12.39%.
2.3.2. 2,20-(1,3-Phenylene) bis (3-ethyl-2-imino-4-phenyl-3H-
thiazole) (4b)
Yield 47%; yellow solid; mp 185–186 °C; FT-IR (KBr) (mmax
/
2.2.6. 3-Allyl-2-(10-naphthylimino)-4-phenyl-3H-thiazole (2f)
cmꢀ1): 3076, 2926, 1610, 1597, 1575, 1499, 1384, 1251, 1199,
1082, 785, 698. 1H NMR (CDCl3, 400 MHz): dH: 1.24 (t, 6H,
J = 6.8 Hz), 3.90 (q, 4H, J = 6.8 Hz), 5.77 (s, 2H), 6.81 (dd, 2H,
J = 7.2, 2 Hz), 6.89 (s, 1H), 7.35 (t, 1H, J = 7.2 Hz), 7.41–7.47 (m,
10H) ppm; 13C NMR (CDCl3, 100 MHz): dc: 14.3, 40.1, 95.5, 113.8,
116.7, 128.6, 128.7, 129.0, 130.5, 131.7, 140.5, 153.0, 160.5 ppm;
Anal. Calcd for C28H26N4S2 (482.66): C, 69.74; H, 5.42; N, 11.60.
Found: C, 69.83; H, 5.49; N, 11.53%.
Yield 71%; white solid; mp 150–152 °C; FT-IR (KBr) (mmax
/
cmꢀ1): 3080, 2922, 1610, 1589, 1577, 1560, 1496, 1413, 1382,
1242, 1230, 1001, 966, 914, 844, 700. 1H NMR (CDCl3, 400 MHz):
dH: 4.62–4.63 (m, 2H), 5.19 (dd, 1H, J = 17.2, 1.2 Hz), 5.30 (dd, 1H,
J = 10.4, 1.2 Hz), 5.83 (s, 1H), 6.03–6.11 (m, 1H), 7.44–7.55 (m,
9H), 7.60 (d, 1H, J = 8.4 Hz), 7.86 (d, 1H, J = 7.8 Hz), 8.27 (d, 1H,
J = 7.8 Hz) ppm; 13C NMR (CDCl3, 100 MHz): dc: 47.7, 96.0, 114.4,
116.6, 122.9, 123.8, 125.0, 126.0, 126.3, 127.8, 128.6, 128.7,
128.9, 129.2, 131.6, 133.0, 134.7, 140.3, 148.2, 159.4 ppm; Anal.
Calcd for C22H18N2S (342.45): C, 77.16; H, 5.29; N, 8.18. Found: C,
77.09; H, 5.36; N, 8.10%.
2.3.3. 2,20-(1,3-Phenylene) bis (3-allyl-2-imino-4-phenyl-3H-thiazole)
(4c)
Yield 55%; yellow solid; mp 185–186 °C; FT-IR (KBr) (mmax
/
2.2.7. 3-Allyl-2-(o-tolylimino)-4-phenyl-3H-thiazole (2g)
cmꢀ1): 3080, 2923, 1591, 1577, 1560, 1496, 1413, 1396, 1413,
1382, 1096, 966, 914, 700, 470. 1H NMR (CDCl3, 400 MHz): dH:
4.48 (d, 4H, J = 4.4 Hz), 5.06 (d, 2H, J = 17.6 Hz), 5.17 (d, 2H,
J = 10.0 Hz), 5.82 (s, 2H), 5.90–5.99 (m, 2H), 6.80 (dd, 2H, J = 8.0,
1.6 Hz), 6.86 (s, 1H), 7.36 (t, 1H, J = 8.0 Hz), 7.39–7.47 (m, 10H)
ppm; Anal. Calcd for C30H26N4S2 (506.65): C, 71.20; H, 5.17; N,
11.05. Found: C, 71.11; H, 5.23; N, 11.14%.
Yield 67%; white solid; mp 150–152 °C; FT-IR (KBr) (mmax
/
cmꢀ1): 3057, 2963, 2916, 1604, 1580, 1504, 1421, 1384, 1251,
1107, 950, 705. 1H NMR (CDCl3, 400 MHz): dH: 2.09 (s, 3H), 4.46
(d, 2H, J = 4.4 Hz), 5.04 (d, 1H, J = 17.2 Hz), 5.19 (d, 1H, J =
10.4 Hz), 5.78 (s, 1H), 5.89–5.97 (m, 1H), 6.61 (t, 1H, J = 7.6 Hz),
7.40–7.47 (m, 5H), 7.80 (d, 1H, J = 8 Hz), 8.32 (t, 1H, J = 7.6 Hz),

116
J. Abbasi Shiran et al. / Journal of Molecular Structure 1039 (2013) 113–118
Table 1
Products 2a–h.
Entry
Ar
Product (2)
Time (h)
4.5
Yielda (%)
72
a
m-Methoxyphenyl
b
c
p-Methoxyphenyl
2
1
76
64
3,4-Dimethoxyphenyl
p-Ethoxyphenyl
p-Ethylphenyl
d
e
3
59
62
3.5
f
1-Naphthyl
2
7
3
71
67
73
g
h
o-Methylphenyl
p-Hydroxyphenyl
a
Isolated yield.
2.3.4. 2,20-(4,40-Ethylenebiphenyl) bis (3-allyl-2-imino-4-phenyl-3H-
thiazole) (6)
In addition, starting from 1,3-phenylenediamine and various
isothiocyanates, dithioureas 3 were synthesized. Reaction between
1,3-phenylenediamine with AITC, ethylisothiocyanate (EITC),
methylisothiocyanate (MITC) at 50–60 °C gave 1,10-(1,3-pheny-
lene)bis(3-allylthiourea), 1,10-(1,3-phenylene)bis(3-ethyllthiourea)
and 1,10-(1,3-phenylene)bis(3-methylthiourea) in excellent yields,
respectively. The reaction between dithioureas 3 with 2-bromo-
acetophenone in refluxing EtOH gave the desired products 4a-c,
in high yields (Scheme 2).
Yield 62%; white solid; mp 185–186 °C; FT-IR (KBr) (mmax
/
cmꢀ1): 3043, 2971, 2929, 2850, 1607, 1595, 1506, 1442, 1242,
1126, 1019, 920, 839, 698. 1H NMR (CDCl3, 400 MHz): dH: 2.92 (s,
2H), 4.46 (d, 2H, J = 4.4 Hz), 5.05 (d, 1H, J = 17.2 Hz), 5.18 (d, 1H,
J = 10.4 Hz), 5.80 (s, 1H), 5.90–5.98 (m, 1H), 7.02 (d, 2H,
J = 8.0 Hz), 7.17 (d, 2H, J = 8.0 Hz), 7.40–7.48 (m, 5H) ppm; Anal.
Calcd for C38H34N4S2 (610.83) C, 74.72; H, 5.61; N, 9.17. Found:
C, 74.83; H, 5.69; N, 9.30%.
All the compounds shown in Tables 1 and 2 were characterized
by spectroscopic methods [FT-IR, 1H NMR and 13C NMR] and ele-
mental analysis. In the present investigation, different structures
were confirmed by appearance of a characteristic C@N stretching
at 1440–1496 cmꢀ1 and complete disappearance of thiourea NHs
absorptions in the IR spectra. A new strong band at 1220–
1285 cmꢀ1 in the IR spectra of compounds showed ring closure
3. Results and discussion
3.1. Synthesis and characterization
1
(CAS). The corresponding H NMR spectra of 3-allyl-2-(30-meth-
The reaction between allylisothiocyanate (AITC) with aromatic
amines at temperatures between 50 and 60 °C in water bath and
under reflux gave N-allyl-N0-substituted thioureas 1 in high yields.
The reaction rate depends on the nature of the corresponding
amine. Depending on the solubility of substituted amines, EtOH
or acetone were employed as solvent for this reaction. We used
EtOH as solvent. Then 1 was condensed with 2-bromoacetophe-
none to afford the allyl-3H-thiazole (2a-h). The target compounds
(2a-h) were obtained by the reaction of corresponding thioureas
with 2-bromoacetophenone in refluxing absolute ethanol. The re-
sults are presented in Table 1.
oxyphenylimino)-4-phenyl-3H-thiazole (2a) showed
a doublet
Table 2
Products 4a–c.
Entry
R
Product
Time (h)
Yielda (%)
1
2
3
Me
Et
Allyl
4a
4b
4c
6
4
6
56
47
55
a
Isolated yield.

J. Abbasi Shiran et al. / Journal of Molecular Structure 1039 (2013) 113–118
117
Scheme 3. Synthesis of 2,20-(4,40-ethylenebiphenyl)bis(3-allyl-2-imino-4-phenyl-3H-thiazole).
Table 3
luteus and Bacillus subtilis, were used to determine antibacterial
properties of the synthesized compounds. Each bacterium was
grown in 3 mL of nutrient broth (Merck) over night at 37 °C and
Antimicrobial activity of (2a–h) and (4a–c).
Conc. of
Antimicrobial activity (zone of inhibition in mm)
compound
(lg/well)
then 50 ll was aseptically transferred to nutrient agar (Merck)
S. enteric
M. luteus
B. subtilis
P. aeruginosa
plates. The suspension was spread on the medium with a sterile
spreader and wells were punched into the medium using the ster-
ile ends of Pasteur pipettes. Each compound was dissolved in
2a
2b
2c
2d
2e
2f
2g
2h
4a
4b
4c
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
4.38
15
22
16
30
10
21
30
24
26
24
29
39
37
7
10
10
14
14
15
16
11
16
18
16
22
20
10
16
11
–
9
–
12
13
-
9
17
–
15
12
18
18
17
10
18
DMSO and 50
ent agar (final concentration, 4.38
romycin and tetracycline disks (containing 15
l
l was dispensed into the wells created in the nutri-
g/well). For comparison, eryth-
g and 30 g of
-
l
12
10
12
9
13
20
13
14
12
14
l
l
antibiotic, respectively) were used. The plates were incubated over
night at 37 °C and zones of inhibition were measured (Table 3).
4. Conclusions
6
Stda
Stdb
30
8
In conclusion, a efficient protocol was developed for the synthe-
sis of novel derivatives of allyl-1,3-thiazoline and bis(1,3-thiazo-
line). The antibacterial activity of newly synthesized compounds
was measured; compounds 2c, 2f, 4b, 4c and 6 showed the most
antibacterial activity. It seems that the bis-structure of compounds
4b, 4c and 6 probably potentiates the enhanced antibacterial activ-
ity. Furthermore, our results show that: (1) An increase in the size
of the alkyl group 4b led to a better bioactivity compared to 2a; (2)
Introduction of allyl group in 4c led to enhanced antibacterial
activity.
ꢀ: Resistant.
a
Tetracycline is used as standard.
Erythromycin is used as standard.
b
(1H) for terminal (alkenyl) CH2 at d 5.18 (J = 17.2 Hz), a doublet
(1H) for terminal (alkenyl) CH2 at d 5.32 (J = 10.4 Hz), a doublet
(2H) for CH2 at d 5.42 (J = 4.8 Hz) and multiples for CH (1H) at d
5.85–5.95 in the allyl group, respectively. CH proton of thiazole
ring appeared as a singlet (1H) at d 5.78 which proved the closure
of thiazole ring.
Bis-allyliminothiazoline 6 was prepared by heating the corre-
sponding dithiourea 5 with 2-bromoacetophenone in ethanol at
50–60 °C for 2 h (Scheme 3). Compound 6 exhibits noticeable anti-
bacterial activities.
Acknowledgment
We are thankful to Research Council of University of Guilan for
partial support of this work.
References
3.2. Determination of antibacterial activity
[1] P. Vicini, A. Geronikaki, K. Anastasia, M. Incerti, F. Zani, Bioorg. Med. Chem. 14
(2006) 3859.
[2] S. Bae, H.G. Hahn, K.D. Nam, H. Mah, J. Comb. Chem. 7 (2005) 7.
Two Gram negative bacteria, Pseudomonas aeruginosa and
Salmonella enterica, and two Gram positive bacteria, Micrococcus

118
J. Abbasi Shiran et al. / Journal of Molecular Structure 1039 (2013) 113–118
[3] S.M. Sondhi, S. Singh, J. Kumar, H. Jamal, P.P. Gupta, Eur. J. Med. Chem. 44 (2009)
1010.
[4] A.K. Chaturvedi, S.S. Pamar, Znd. J. Pharm. 34 (1972) 72.
[5] (a) X.X. Zhu, Q.S. Yu, R.G. Gulter, C.W. Culmess, H.W. Holloway, D.K. Lahiri, M.P.
Mattson, N.H. Greig, J. Med. Chem. 45 (2002) 5090;
[6] H. Yu, L. Shao, J. Fang, J. Organometal. Chem. 692 (2007) 991;
F. Nagasaki, T. Yamada, E. Takahashi, Y. Kitagawa, R. Hatano, Jpn. Kokai Tokkyo
Koho JP 63250371, 18/10/1988.;
F. Nagasaki, T. Yamada, E. Takahashi, Y. Kitagawa, R. Hatano, Chem. Abstr. 110
(1989) 192810.
(b) D.-S. Kim, Y.-M. Jeong, I.-K. Park, H.-G. Hahn, H.-K. Lee, S.-B. Kwon, S.J. Yang,
U.D. Sohn, K.-C. Park, Biol. Pharm. Bull. 30 (2007) 180.
[7] A. Saeed, U. Shaheen, A. Hameed, F. Kazmi, J. Fluorine Chem. 131 (2010) 333.
[8] M.-H. Shih, F.-Y. Ke, Bioorg. Med. Chem. 12 (2004) 4633.