Ultrasound and water-mediated synthesis of bis-thiazoles catalyzed by Fe(SD)3 as Lewis acid-surfactant-combined catalyst

Article abstract of DOI:10.1080/17415993.2017.1400033

Preparation of bis-aminothiazoles under different conditions including synthesis in EtOH under ultrasound irradiation and also in water in the presence of Fe(SD)₃ as Lewis acid-surfactant-combined catalyst (LASC) under ultrasound irradiation has been studied. The results were compared with the traditional reflux method. Also, the results confirmed the efficiency of the synthesis in water and under ultrasound irradiation technique. Moreover, the antibacterial activity of products was investigated using the well-diffusion method against bacterial strains including Micrococcus luteus, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis. All of the products showed good antibacterial activity against M. luteus and E. coli. Most of the products showed antibacterial activity higher than erythromycin against M. luteus, E. coli, and B. subtilis.

Full text of DOI:10.1080/17415993.2017.1400033

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Ultrasound and water-mediated synthesis of
bis-thiazoles catalyzed by Fe(SD)3 as Lewis acid-
surfactant-combined catalyst
Jafar Parvizi, Nosrat O. Mahmoodi & Fateme Ghanbari Pirbasti
To cite this article: Jafar Parvizi, Nosrat O. Mahmoodi & Fateme Ghanbari Pirbasti (2017):
Ultrasound and water-mediated synthesis of bis-thiazoles catalyzed by Fe(SD)3 as Lewis acid-
surfactant-combined catalyst, Journal of Sulfur Chemistry, DOI: 10.1080/17415993.2017.1400033
To link to this article: http://dx.doi.org/10.1080/17415993.2017.1400033
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Date: 13 November 2017, At: 06:21

JOURNAL OF SULFUR CHEMISTRY, 2017
https://doi.org/10.1080/17415993.2017.1400033
Ultrasound and water-mediated synthesis of bis-thiazoles
catalyzed by Fe(SD)3 as Lewis acid-surfactant-combined
catalyst
Jafar Parvizia, Nosrat O. Mahmoodib and Fateme Ghanbari Pirbastib
aDepartment of Chemistry, University of Guilan, Rasht, Iran; bDepartment of Chemistry, Faculty of Sciences,
University of Guilan, Rasht, Iran
ABSTRACT
ARTICLE HISTORY
Received 30 July 2017
Accepted 29 October 2017
Preparation of bis-aminothiazoles under different conditions includ-
ing synthesis in EtOH under ultrasound irradiation and also in
water in the presence of Fe(SD)3 as Lewis acid-surfactant-combined
catalyst (LASC) under ultrasound irradiation has been studied.
The results were compared with the traditional reflux method.
Also, the results confirmed the efficiency of the synthesis in
water and under ultrasound irradiation technique. Moreover, the
antibacterial activity of products was investigated using the well-
diffusion method against bacterial strains including Micrococcus
luteus, Escherichia coli, Pseudomonas aeruginosa and Bacillus sub-
tilis. All of the products showed good antibacterial activity against
M. luteus and E. coli. Most of the products showed antibacterial
activity higher than erythromycin against M. luteus, E. coli, and
B. subtilis.
KEYWORDS
Bis-aminothiazole;
antimicrobial activity;
ultrasound; Fe(SD)3; green
synthesis
CONTACT Nosrat O. Mahmoodi
mahmoodi@guilan.ac.ir, nosmahmoodi@gmail.com
Department of Organic
Chemistry, Faculty of Sciences, University of Guilan, PO Box 41335-1914, Rasht, Iran
This article makes reference to supplementary material available on the publisher’s website at https://doi.org/10.1080/
17415993.2017.1400033.
© 2017 Informa UK Limited, trading as Taylor & Francis Group

2
J. PARVIZI ET AL.
1. Introduction
Thiazoles are important heterocyclic moiety found in drugs, e.g. sulfathiazole, ritonavir,
penicillin, abafungin, and tiazofurin. Various biological activities are attributed to the
aminothiazoles or compounds bearing this moiety such as antitubercular activity [1],
CHK1 inhibitors [2], phosphoinositide 3-kinase γ inhibitor [3], antiplatelet agent [4], and
antimycobacterial and antiplasmodial agent [5].
Recently, some studies are paid to the synthesis of aminothiazoles, e.g. thiourea and
substituted ketones reacted in the presence of NaICl2 under reflux condition in THF
[6] and cyclization of α-halo ketones with ammonium thiocyanate in the presence of
N-methylimidazole (10 mol%) in water–alcohol media [7]. However, some methods suf-
fer from many drawbacks including the use of toxic solvents, by-products and long
reaction times.
Green chemistry has attracted great attention of scientists due to its environmentally
benign methods. One of the methods in green chemistry is using water as a nontoxic, read-
ily available, low-cost, environmentally benign, non-flammable, polar and clean solvent
instead of harmful solvents [8,9]. Furthermore, using a green and efficient source of energy
such as ultrasound irradiation is important from both economic and ecological points
of view. Ultrasound prompted synthesis have some advantageous such as high yield, low
temperature of the reaction, faster reaction, and minor percentage of by-products [10,11].
In continuation to our recent studies in the green synthesis of heterocyclic compounds
[12–18], using ultrasound irradiation [19,20], here a green synthesis of bis-thiazoles with
alkyl linkages beginning with the reaction of bis-α-bromoketones and thiourea under
ultrasound irradiation in different conditions are investigated.
2. Results and discussion
2.1. Chemistry
The synthesis of bis-thiazoles 5a–g and thiaozles 5h,i was investigated under ultrasound
irradiation via methods B and C and the results were compared with recently reported
method A [21] (Scheme 1). Bis-acetophenons and their α-bromo derivatives 3a–g were
prepared according to the literature [21,22]. Finally, the reaction of thiourea 4 with
α-bromo derivatives 3a–g was investigated under methods B and C.
Also, preparation of aminothiazoles 5h,i was investigated under optimized reaction
condition (Scheme 2).
The synthesis of compound 5a as a model reaction was investigated under ultrasound
irradiation at different temperatures. According to Table 1, synthesis of compound 5a was
investigated in EtOH as solvent under ultrasound irradiation and at different temperatures
from 30°C to 60°C. As the temperature was increased from 30°C to 60°C the yield of the
reaction was improved and the product was obtained in shorter reaction time (entry 4,
Table 1). These results confirm the efficiency of ultrasound irradiation in comparison to
traditional condition (method A). Under ultrasound irradiation cavitation phenomenon
occurs and lead to hot spots with high temperatures [23].
Recently, the efficient role of Fe(SD)3 as a Lewis acid-surfactant-combined catalyst
(LASC) in the synthesis of heterocyclic compounds was reported in [20,24]. Fe(SD)3 was
prepared in situ from the reaction of sodium dodecyl sulfate and FeCl3.6H2O in water.

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 1. General procedure for the synthesis of bis-thiazoles 5a–g.
Scheme 2. Optimized reaction condition for preparation of 5h,i.
Table 1. Optimization of the reaction condi-
tion according to method B.
Entry
Temperature (°C)
Time (min)
Yield %
1
2
3
4
30
40
50
60
70
50
35
20
75
77
80
85
In consideration green reaction medium, e.g. using H2O as a solvent, synthesis of com-
pound 5a was attempted as a model reaction under ultrasound irradiation at different
temperatures and in the presence of different amounts of Fe(SD)3 in H2O. For optimization
of method C, the synthesis of 5a was studied under different temperatures and different
amounts of Fe(SD)3 under ultrasound irradiation in H2O (Table 2). Since, most of the
organic compounds are insoluble or have low solubility in H2O, Micellar systems can be
used to overcome the solubility problems [25,26]. The increase of the temperature from

4
J. PARVIZI ET AL.
Table 2. Optimization of the reaction for method C.
Entry
Temperature (°C)
Amount of Fe(SD)3 (mol%)
Time (min)
Yield %
1
2
3
4
5
6
7
30
40
50
60
60
60
60
10
10
10
10
20
30
40
90
75
50
35
17
15
15
60
65
69
77
78
80
80
H2N
H2N
NH2
+
Fe3
ultrasound
irradiation
O
N
S
S
Br
FeCl3.6H2O
60 °C
Br
S
S
N
O
3+Fe
H N
2
NH2
NH2
SO3Na
= SDS
hydrophobic tail
hyrophilic head
Scheme 3. Entire reaction taking place in the micelle.
30°C to 60°C in the presence of Fe(SD)3(10 mol%) led to the product in shorter reaction
time and higher yield. Furthermore, the temperature of the reaction was set at 60°C and
the synthesis of 5a was studied under 10–40 mol% of Fe(SD)3. The optimum reaction
condition was obtained see entry 6. The efficient dual role of Fe(SD)3 can be due to the for-
mation of micelles in H2O with the hydrophobic core and the hydrophilic outer surface.
The organic reactants are capsulated in the hydrophobic core with the diameter of 10–28
Å [28] so this provides a proper place for performing the reaction. Also, Fe3+ as Lewis acid
increases nucleophilic addition of NH2 to carbonyl moiety (Scheme 3).
Moreover, the scope of these methods has been extended to the synthesis of compounds
5a–i (Table 3). Methods A, B, and C led to products in reasonable yields 70–90%, 75–87%,
and 72–87%, respectively. Products were obtained in short reaction times 10–30 and 10–20
min under ultrasound irradiation using methods B and C, respectively. These results con-
firm the efficient synthesis of compounds 5a–i using methods B and C. Moreover, Fe(SD)3
as LASC has improved the yield and rate of the reaction in H2O. Recently, synthesis of
bis-thiazoles in EtOH/1,4-dioxane at 3–5 h was performed under reflux condition [28]. In
comparison to the reported method under ultrasound irradiation methods B and C led to
products in shorter reaction time (10–20 min) through the green method.
The synthesis of the compounds was confirmed by melting points and compared with
the reported data and IR spectra [21]. In IR spectra, the stretching vibration of the

JOURNAL OF SULFUR CHEMISTRY
5
Table 3. Synthesis of thiazoles using methods A, B, and C.
MethodAreflux/EtOH
Method B ultrasound/EtOH/60°C
MethodCultrasound/H2O/Fe(SD)3/60°C
Compound
Yield%
m.p. (°C)
Time (min)
Yield%
m.p. (°C)
Time (min)
Yield%
m.p. (°C)
5a
5b
5c
5d
5e
5f
5g
5h
5i
72
80
80
78
80
75
70
90
80
231–234
229–232
230–232
229–231
230–232
230–233
231–234
204–207
149–153
20
25
25
20
18
20
25
10
10
85
85
80
82
85
85
80
87
75
233–235
231–233
229–231
231–234
231–233
230–232
230–233
206–209
150–154
15
17
17
15
16
15
19
10
10
80
87
85
85
80
75
75
85
72
232–234
230–232
229–232
230–234
231–233
230–234
231–232
206–209
150–154
amine group (NH2) and C–N appeared at 3482–3123 and 1055–1096 cm−1, respectively.
Moreover, the stretching vibration of C =N appeared at 1509–1610 cm−1
.
The signals of both OCH2, and OCH2CH2 protons in compounds 5a and 5b appear
as two sets of multiple signals (as clearly indicated in expanded spectra). The 13C NMR
of both 5a and 5b indicated a correct set of pecks 9 and 10, respectively. The H NMR
1
also indicates a correct set of protons. However, due to hydrogen bonding, intermolecu-
lar aggregation between protons of NH2 and thiazole nitrogens a subtle conformational
rotation from a symmetrical structure was observed.
2.2. Antimicrobial activity
Antibacterial activity of products 5a–i was investigated using well-diffusion assay against
Gram-positive bacterial strains including Micrococcus luteus and Bacillus subtilis and
Gram-negative bacterial strains including Escherichia coli and Pseudomonas aeruginosa
(Table 4). Products were used at a concentration of 1000 μg/mL in DMSO as the nega-
tive control. Positive controls were tetracycline and erythromycin. Interestingly, bacterial
strains including M. luteus and E. coli were sensitive to all products. However, most of
the products had antibacterial activity against Ps. aeruginosa and B. subtilis. Moreover, M.
luteus was the most sensitive bacterial strain with the range of zone of inhibition from
Table 4. Results of antibacterial assay of compounds 5a-–i
expressed as zone of inhibition in mm.
Zoneof inhibition (mm)
Compound
Ps. aeruginosa
B. subtilis
M. luteus
E. coli
5a
5b
5c
5d
5e
5f
5g
5h
8
–
–
–
7
7
13
–
–
–
19
14
10
–
12
–
15
17
14
–
28
24
19
19
27
19
29
19
15
–
17
15
9
9
15
12
16
16
15
–
5i
DMSO
Tetracycline
Erythromycin
23
15
21
17
25
19
23
15

6
J. PARVIZI ET AL.
29 to 15 mm. Furthermore, products 5a, 5e and 5g showed higher antibacterial activity
against M. luteus in comparison to tetracycline and also, all products except 5i were most
active or had equal activity against M. luteus in comparison to erythromycin. Moreover, all
products possessed antibacterial activity against E. coli with the zone of inhibition ranged
from 17 to 9 mm and all products except 5c, 5d and 5f showed antibacterial activity higher
than or similar as erythromycin. While none of them had antibacterial activity compara-
ble to tetracycline. All products except 5d and 5f showed antibacterial activity against B.
subtilis and only products 5a and 5h showed antibacterial activity higher than or equal to
erythromycin. Only products 5a, 5e, 5f, and 5g showed antibacterial activity against Ps.
aeruginosa while their activity was not comparable to tetracycline and erythromycin.
Also, in this study gram-positive bacterial strain M. luteus was most sensitive to prod-
ucts. Structurally, gram-negative bacteria have a lipopolysaccharide layer as the outer layer
which excludes certain drugs and antibiotics from penetrating the cell and so are more
resistant to antibiotics than are gram-positive bacteria. Nevertheless, all products showed
activity against E. coli a gram-negative bacteria strain.
3. Conclusion
In conclusion, efficient and convenient synthetic methods under ultrasound (method B)
and also in aqueous media in the presence of Fe(SD)3 (30 mol%) as the LASC (method C)
have been developed for the synthesis bis-thiazoles. The main benefits of these methods are
easy set-up, simplicity, high yields, safety, environmentally benign and short reaction time.
Also, most of the compounds possessed good antibacterial activity against both gram-
positive and -negative bacterial strains. Moreover, higher antibacterial activity of some
compounds in comparison to tetracycline and erythromycin was interesting.
4. Experimental
4.1. Material and methods
Chemicals were purchased from Merck and Fluka and used as purchased. Melting points
were measured on an Electro-thermal 9100 apparatus and are uncorrected. Ultrasound
apparatus Eurosonic Astra 4D (220 V, 60 Hz frequency) was used. The IR spectra were
1
recorded on Shimadzu 470 spectrometer. The H NMR and 13C NMR spectra were
obtained on a Bruker Avance 400 and 100 MHz spectrometer, respectively. DMSO-d6 was
used as solvent.
4.2. General procedure for the synthesis of bis-thiazoles 5a–h and thiazoles 5i,j
Compounds 3a–g were prepared according to the literature [21].
Method A: according to the literature [21].
Method B: To a test tube was added 3a–g (1 mmol), thiourea 4 (2 mmol) and EtOH
(7 mL) and was placed in an ultrasound bath at 60°C for the required time. The progress of
the reaction was monitored by TLC (EtOAc:n-hexane 1:3). After completion of the reac-
tion, the solid was filtered, washed with water and EtOH. For the preparation of products
5h,i compounds 6h,i (1 mmol) and thiourea 4 (1 mmol) were used.

JOURNAL OF SULFUR CHEMISTRY
7
Method C: To a test tube was added compound 3a–g (1 mmol), thiourea 4 (2 mmol),
Fe(SD)3 (30 mol%) and water (7 mL) and was placed in an ultrasound bath at 60°C
for the required time. The progress of the reaction was monitored by TLC (EtOAc:n-
hexane 1:3). After completion of the reaction, the solid was filtered, washed with water
and EtOH. Compounds 6h,i (1 mmol) and thiourea 4 (1 mmol) were used for preparation
of products 5h,i.
4.2.1. 4,4ꢀ-((Butane-1,4-diylbis(oxy))bis(4,1-phenylene))bis(thiazol-2-amine) (5a)
Method B; Yield: 85%; m.p.: 233–235°C, Method C; Yield: 80%; m.p.: 232–234°C, FT-IR
(KBr): 3379, 3271 (N–H stretch), 3080 (aromatic C–H stretch), 2937, 2866 (aliphatic C–H
stretch), 1625 (C9N stretch), 1606, 1577, 1510 (aromatic C–C stretch), 1469 (C–H bending,
CH2), 1251, 1012 (C–O stretch), 1186 (C–N stretch), 833 (aromatic C–H out of plane bend-
ing) cm−1. 1H NMR (400 MHz, DMSO-d6): δ; 7.93 (d, J = 8.8 Hz, 2H), 7.71 (d, J = 8.8 Hz,
2H), 7.04 (dd, J = 8.8, 1.6 Hz, 2H), 6.98 (s, 1H), 6.93 (d, J = 8.8 Hz, 2H), 6.83 (s, 1H),
4.19 (bro, 2H), 4.06 (bro, 2H), 1.92 (bro, 2H), 1.90 (bro, 2H) ppm. 13C NMR (100 MHz,
DMSO-d6): δ; 170.3, 163.0, 159.8, 131.1, 127.3, 114.9, 103.3, 68.0, 26.3 ppm. Anal. calcd.
for C22H22N4O2S2: C, 60.25; H, 5.06; N, 12.78. Found: C, 60.23; H, 5.04; N, 12.77. HRMS:
m/z for C22H22N4O2S2; calculated 438. 1184; found:438.1190.
4.2.2. 4,4ꢀ-((Pentane-1,5-diylbis(oxy))bis(4,1-phenylene))bis(thiazol-2-amine) (5b)
Method B; Yield: 85%; m.p.: 231–233°C, Method C; Yield: 87%; m.p.: 230–232°C, FT-
IR (KBr): 3363, 3267 (N–H stretch), 3109 (aromatic C–H stretch), 2939, 2884 (aliphatic
C–H stretch), 1625 (C9N stretch), 1577, 1539, 1506 (aromatic C–C stretch), 1463 (C–H
bending, CH2), 1255 (C–O stretch), 1182 (C–N stretch), 831 (aromatic C–H out of plane
1
bending) cm−1. H NMR (400 MHz, DMSO-d6): δ; 7.72 (d, J = 8.4 Hz, 1H), 7.65 (dd,
J = 8.8, 2 Hz, 3H), 7.20 (d, J = 8.8 Hz, 1H,), 7.12 (s, 1H,), 7.06–7.02 (m, 3H), 4.15–4.10 (m,
2H), 4.07–4.02 (m, 2H), 1.92–1.83 (m, 4H), 1.65–1.59 (m, 2H) ppm. 13C NMR (100 MHz,
DMSO-d6): δ; 170.3, 159.8, 150.0, 130.4, 127.7, 114.3, 109.8, 68.07, 28.6, 22.5 ppm. Anal.
calcd. for C23H24N4O2S2: C, 61.04; H, 5.35; N, 12.38. Found: C, 61.03; H, 5.34; N, 12.37.
HRMS: m/z for C23H24N4O2S2; calculated 452.1341; found: 452.1345.
4.2.3. 4,4ꢀ-((Hexane-1,6-diylbis(oxy))bis(4,1-phenylene))bis(thiazol-2-amine) (5c)
Method B; Yield: 80%; m.p.: 229–231°C, Method C; Yield: 85%; m.p.: 229–232°C, FT-
IR (KBr): 3379, 3271 (N-H stretch), 3080 (aromatic C–H stretch), 2937, 2866 (aliphatic
C–H stretch), 1625 (C=N stretch), 1606, 1577, 1510 (aromatic C–C stretch), 1469 (C–H
bending, CH2), 1251, 1012 (C–O stretch), 1186 (C–N stretch), 833 (aromatic C–H out of
1
plane bending) cm−1. H NMR (400 MHz, DMSO-d6): δ; 7.92 (d, J = 8.8 Hz) and 7.65
(d, J = 8.6, 2.2 Hz), 7.07–7.01 (m, 6H), 4.09–4.02 (m, 4H), 1.76 (s, 4H), 1.49 (s, 4H) ppm.
13C NMR (100 MHz, DMSO-d6): δ; 169.4, 162.5, 152.0, 130.9, 129.4, 115.1, 90, 69.6, 26.9,
14.5 ppm. Anal. calcd. for C24H26N4O2S2: C, 61.78; H, 5.62; N, 12.01. Found: C, 61.75; H,
5.61; N, 12.01. HRMS: m/z for C24H26N4O2S2; calculated 466.1497; found: 466.1491.
4.2.4. 4,4ꢀ-((Butane-1,4-diylbis(oxy))bis(3,1-phenylene))bis(thiazol-2-amine) (5d)
Method B; Yield: 82%; m.p.: 231-234°C, Method C; Yield: 85%; m.p.: 230–234°C, FT-IR
(KBr): 3440, 3274 (N–H stretch), 3109 (aromatic C–H stretch), 2923, 2854 (aliphatic C–H
stretch), 1635 (C=N stretch), 1558 (aromatic C–C stretch), 1471 (C–H bending, CH2),

8
J. PARVIZI ET AL.
1232, 1035 (C–O stretch), 1174 (C–N stretch), 854, 811, 740 (aromatic C–H out of plane
1
bending) cm−1. H NMR (400 MHz, DMSO-d6): δ; 7.65 (d, J = 8.8 Hz, 2H), 7.403 (t,
J = 7.8 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H), 7.20 (d, J = 1.6 Hz, 2H), 7.07–7.02 (m, 8H) ppm.
13C NMR (100 MHz, DMSO-d6): δ; 169.6, 158.3, 138.0, 135.4, 134.5, 129.8, 118.3, 112.4,
107.6, 68.2, 25.6 ppm. Anal. calcd. for C22H22N4O2S2: C, 60.25; H, 5.06; N, 12.78. Found:
C, 60.23; H, 5.05; N, 12.74. HRMS: m/z for C22H22N4O2S2; calculated 438.1184; found:
438.1191.
4.2.5. 4,4ꢀ-((Pentane-1,5-diylbis(oxy))bis(3,1-phenylene))bis(thiazol-2-amine) (5e)
Method B; Yield: 85%; m.p.: 231–233°C, Method C; Yield: 80%; m.p.: 231–233°C, FT-
IR (KBr): 3425, 3369 (N-H stretch), 3109 (aromatic C–H stretch), 2925, 2854 (aliphatic
C–H stretch), 1633 (C9N stretch), 1573 (aromatic C–C stretch), 1479 (C–H bending,
CH2), 1232, 1035 (C–O stretch), 1174 (C–N stretch), 854, 811, 732 (aromatic C–H out of
plane bending) cm−1. 1H NMR (400 MHz, DMSO-d6): δ; 7.63 (d, J = 8.8 Hz, 1H), 7.37
(t, J = 8 Hz, 2H), 7.32–7.30 (m, 3H), 7.24 (s, 2H), 7.20 (d, J = 2.8 Hz, 2H), 7.06–6.97
(m, 4H), 4.06 (t, J = 6.4 Hz, 4H), 1.86–1.79 (m, 4H), 1.65–1,61 (m, 2H) ppm. 13C NMR
(100 MHz, DMSO-d6): δ; 170.2, 159.4, 141.1, 134.5, 138.6, 118.3, 115.6, 112.2, 103.4, 68.1,
26.8, 22.7 ppm. Anal. calcd. for C23H24N4O2S2: C, 61.04; H, 5.35; N, 12.38. Found: C,
61.02; H, 5.33; N, 12.35. HRMS: m/z for C23H24N4O2S2; calculated 452.1134; found:
438.1141.
4.2.6. 1,6-Diylbis(oxy))bis(3,1-phenylene))bis(thiazol-2-amine) (5f)
Method B; Yield: 85%; m.p.: 230–232°C, Method C; Yield: 75%; m.p.: 230–234°C, FT-
IR (KBr): 3419, 3265 (N–H stretch), 3099 (aromatic C–H stretch), 2933, 2858 (aliphatic
C–H stretch), 1635 (C9N stretch), 1558, 1523 (aromatic C–C stretch), 1461 (C–H bending,
CH2), 1232, 1039 (C–O stretch), 1174 (C–N stretch), 848, 810 (aromatic C–H out of plane
bending) cm−1. 1HNMR (400 MHz, DMSO-d6): δ; 7.69–7.61 (m, 4H), 7.17 (d, J = 2.8 Hz,
2H), 7.08 (s, 4H), 7.06–7.02 (m, 4H), 4.02 (t, J = 6.2 Hz, 4H), 1.74 (s, 4H), 1.47 (s, 4H) ppm.
13C NMR (100 MHz, DMSO-d6): δ; 169.7, 158.4, 137.5, 134.5, 131.4, 128.1, 118.3, 115.6,
107.7, 68.7, 28.9, 25.6 ppm. Anal. calcd. for C24H26N4O2S2: C, 61.78; H, 5.62; N, 12.01.
Found: C, 61.76; H, 5.59; N, 12.01. HRMS: m/z for C24H26N4O2S; calculated 466.1497;
found: 466.1490.
4.2.7. 4,4ꢀ-(((1,4-Phenylenebis(methylene))bis(oxy))bis(3,1-phenylene))bis(thiazol-2-
amine) (5g)
Method B; Yield: 80%; m.p.: 230–233°C, Method C; Yield: 75%; m.p.: 231–232°C, FT-
IR (KBr): 3313, 3176 (N–H stretch), 3068 (aromatic C–H stretch), 1625 (C=N stretch),
1541 (aromatic C–C stretch), 1425 (C–H bending, CH2), 1242, 1076 (C–O stretch),
1145 (C–N stretch), 898, 819, 763, 671 (aromatic C–H out of plane bending) cm−1
.
1H NMR (400 MHz, DMSO-d6): δ; 8.30–6.63 (m, 18H), 4.15 (s, 4H) ppm. 13C NMR
(100 MHz, DMSO-d6): δ; 169.3, 162.9, 159.0, 140.8, 139.6, 135.3, 129.8, 121.0, 115.3, 114.7,
100.9, 68.0 ppm. Anal. calcd. for C26H22N4O2S2: C, 64.18; H, 4.56; N, 11.51. Found: C,
64.17; H, 4.54; N, 11.50. HRMS: m/z for C26H22N4O2S2; calculated 486.1184; found:
486.1178.

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4.2.8. 4-(4-Methoxyphenyl)thiazol-2-amine (5h)
Method B; Yield: 87%; m.p.: 206–209°C [29], Method C; Yield: 85%; m.p.: 206–209°C, FT-
IR (KBr): 3436, 3356 (N–H stretch), 3115 (aromatic C–H stretch), 2934, 2835 (aliphatic
C–H stretch), 1602 (C9N stretch), 1520, 1468 (aromatic C–C stretch), 1327, 1023 (C–O
stretch), 1172 (C–N stretch), 832 (aromatic C–H out of plane bending) cm−1. 1H NMR
(400 MHz, DMSO-d6): δ; 7.61 (d, J = 8 Hz, 2H), 7.05 (d, J = 8 Hz, 2H), 7.00 (s, 2H), 6.90
(s, 1H), 3.70 (s, 3H).ppm. 13C NMR (100 MHz, DMSO-d6): δ; 168.3, 160.9, 150.0, 128.8,
125.6, 114.3, 101.8, 55.8 ppm. Anal. calcd. for C10H10N2OS: C, 58.23; H, 4.89; N, 13.58.
Found: C, 58.25; H, 4.91; N, 13.62. HRMS: m/z for C10H10N2OS; calculated 206.0514;
found: 206.0521.
4.2.9. 4-Phenylthiazol-2-amine (5i)
Method B; Yield: 75%; m.p.: 150–154°C [30], Method C; Yield: 70%; m.p.: 150–154°C, FT-
IR (KBr): 3416 (N–H stretch), 3058 (aromatic C–H stretch), 2925, 2860 (aliphatic C–H
stretch), 1620 (C9N stretch), 1516, 1442 (aromatic C–C stretch), 1327, 1275 (C–O stretch),
1
1140 (C–N stretch), 766, 693 (aromatic C–H out of plane bending) cm−1. H NMR
(400 MHz, DMSO-d6): δ; 7.81 (d, J = 8 Hz, 2H), 7.47–7.45 (m, 1H), 7.39 (t, J = 6.0 Hz,
2H), 7.00 (s, 2H), 6.90 (s, 2H).ppm. 13C NMR (100 MHz, DMSO-d6): δ; 168.00, 150.9,
133.0, 129.8, 128.6, 127.3, 101.8, ppm. Anal. calcd. C9H8N2S: C, 61.34; H, 4.58; N, 15.90.
Found: C, 61.36; H, 4.55; N, 15.92. HRMS: m/z for C9H8N2S; calculated 176.0408; found:
176.0414.
4.3. Antibacterial assay
Each compound was prepared in DMSO at the concentration of 1000 μg/mL. The bacterial
isolates were grown at 37°C in nutrient broth medium. Then, the inocula (50 μL) were
poured on nutrient agar plates and were spread on the agar surface using a sterile spreader.
Wells were cut into the plates and each well received 30 μL of the tested compounds. The
plates were incubated at 37°C for 24 h. The one of inhibition was measured in mm. DMSO
was used as negative control. Tetracycline and erythromycin were used as positive controls.
Acknowledgements
The authors are grateful to the Research Council of University of Guilan for financial support of this
work. Also, the authors appreciate the support of M. Rasa from Department of Biology, Faculty of
Sciences, University of Guilan for antibacterial assay.
Disclosure statement
No potential conflict of interest was reported by the authors.
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