Effective preparation of 5,5’-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one) in an aqueous fluoroalcohol solvent system under ultrasound irradiation at room temperature

Article abstract of DOI:10.1016/j.cclet.2017.01.015

A green and convenient approach for the synthesis of a series of 5,5'-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one) by the reaction of aryl aldehydes, monochloroacetic acid and ammonium thiocyanate in water/trifluoroethanol(TFE) (1:1) under ultrasound irradiation at room temperature is described. This method provides several advantages such as environmental friendliness, shorter time, excellent yields, and simple work-up procedure.

Full text of DOI:10.1016/j.cclet.2017.01.015

Accepted Manuscript
Title: Effective preparation of
5,5’-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one) in an
aqueous fluoroalcohol solvent system under ultrasound
irradiation at room temperature
Authors: Mohammad Reza Poor Heravi, Mozhdeh Naghilou
PII:
S1001-8417(17)30037-2
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.cclet.2017.01.015
CCLET 3964
To appear in:
Chinese Chemical Letters
Received date:
Revised date:
Accepted date:
5-11-2016
10-1-2017
16-1-2017
Please cite this article as: Mohammad Reza Poor Heravi, Mozhdeh Naghilou, Effective
preparation of 5,5’-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one) in an aqueous
fluoroalcohol solvent system under ultrasound irradiation at room temperature, Chinese
Chemical Letters http://dx.doi.org/10.1016/j.cclet.2017.01.015
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Original article
Effective preparation of 5,5'-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one) in an
aqueous fluoroalcohol solvent system under ultrasound irradiation at room
temperature
Mohammad Reza Poor Heravi*, Mozhdeh Naghilou
Department of Chemistry, Payame Noor University, PO Box 19395-3697, Tehran, Iran
 Corresponding author.
E-mail address: mrheravi@yahoo.com, heravimr@gmail.com

Graphical Abstract
A synthesis of 5,5'-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one) using trifluoroethanol (TFE) as an efficient and recyclable
medium in promoting one-pot, pseudo five component reaction is described.
ABSTRACT
A green and convenient approach for the synthesis of a series of 5,5'-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one) by the reaction of aryl aldehydes,
monochloroacetic acid and ammonium thiocyanate in water / trifluoroethanol(TFE) (1:1) under ultrasound irradiation at room temperature is described. This
method provides several advantages such as environmental friendliness, shorter time, excellent yields, and simple work-up procedure.
Keywords: Multicomponent reaction Hydrogen bonding Trifluoroethanol (TFE) Ultrasound irradiation Bis(4-hydroxythiazole-2(3H)-one)
1. Introduction
In recent years, focus on green chemistry using environmentally benign reagents and reaction conditions is one of the most
fascinating developments in synthesis of widely used organic compounds [1,2]. The use of fluorinated solvents has recently received a
great deal of attention as potential new media for organic synthesis [3]. Owing to their unique physicochemical properties (high
hydrogen bonding donor's ability, nonvolatility, nonflammability, polarity, high ionizing power, and low nucleophilicity), fluorinated
alcohols modify the course of reactions when they are used as solvent, allowing reactions which usually require the use of added
reagents or metal catalysts to be carried out under neutral and mild conditions [4, 5]. The most commonly used and cheapest
fluorinated alcohols are 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) low toxicity [6]. Ultrasound, an
efficient and virtually innocuous means of activation in synthetic chemistry, has been employed for decades with various successes.
This high-energy induces new reactivity leading to the formation of unexpected chemical species. The remarkable phenomenon of
cavitation makes sonochemistry unique. The effects of ultrasound observed during organic reaction are due to cavitation, a physical
process that creates, enlarges, and implodes gaseous and vaporous cavities in an irradiated liquid. Cavitation induces very high local
temperatures and pressures inside the bubbles, leading to turbulent flow of the liquid and enhances mass transfer. When compared to
conventional methods, ultrasound-accelerated chemical reactions can give high yields in shorter reaction times and milder conditions
[7]. Because of these advantages, ultrasound irradiation has been used for the synthesis of a wide variety of organic compounds [8].
Organic compounds containing five-membered aromatic heterocyclic rings form a wide range of compounds in the nature and often
play an important role in diverse biochemical processes. Consequently, aromatic heterocycles such as thiophenes, benzothiophene
derivatives, and their reduced forms are important structural fragments in many pharmaceutical and chemical compounds. Thiophenes
and thiazole compounds have been found to indicate nematocidal, insecticidal, antibacterial, antifungal, antiviral, and antioxidant
activity [9–15]. Tetrahydrothiophene is an important building block of a large quantity of compounds that are very interesting from the
point of view of biological activity. Its derivatives have exhibited antisecretory and antiulcer activities [16]. The copper nanoparticles
in an ionic liquid were employed as a recyclable catalyst for the synthesis of bis-(4-hydroxy-2-oxothiazolyl)methanes in excellent
yields and in short reaction time [17]. In particular, it is found in structures of nucleoside analogs and certain compounds where the
sulfur atom is in the ring, such as sulfimides, salicinol, and kotalanol, which are excellent glycosidase inhibitors [18–20]. We report
here a novel method for preparation of 5,5'-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one) via one-pot pseudo five-component
condensation of monochloroacetic acid (2 equiv.), ammonium thiocyanate (2 equiv.), and aromatic aldehydes (1 eq) in
trifluoroethanol(TFE)/water (1:1) under ultrasound irradiation at room temperature.
2. Results and discussion
To find out the suitable conditions for the reaction, a series of experiments were performed with the standard reaction of
monochloroacetic acid, ammonium thiocyanate, and 4-chlorobenzaldehyde (4g) as a model reaction (Scheme 1).

To find an appropriate reaction medium for the synthesis of 5,5'-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one), one-pot pseudo-
five component reaction of monochloroacetic acid (2 mmol), ammonium thiocyanate (2 mmol) and 4-chlorobenzaldehyde (1 mmol) as
a model reaction by detecting the efficiency of several classic solvents chosen as the for comparison with sonication conditions. When
the reaction was carried out under solvent free conditions at room temperature and 110 oC, we found 5% and 10% product (4g) (entries
10 and 11, Table 1). Nevertheless, the most dramatic improvement was observed when the solvent were switched from H2O to
H2O/EtOH and TFE to TFE/EtOH. Therefore, the volume ratio of H2O/EtOH and TFE/EtOH were examined and the best results were
obtained by carrying out the reaction in H2O/EtOH and TFE/EtOH with a ratio of 1:1 (v/v) (entries 12-18, Table 1). In order to verify
the effect of ultrasound irradiation, the reaction was also performed in mentioned solvents by high stirring alone under silent condition
(Table 1). As shown in Table 1, in all cases, the experimental results show that the yields of the products are lower than sonication
within same reaction times. Based on the results of this study, it’s clear that the ultrasound improves the yields of products. In our
opinion, TFE act as Bronsted acid and play a significant role in increasing the electrophilic character of the electrophiles.
In order to investigate the effect of the ultrasonic intensity, power on the reaction, the reaction was also performed at 20%, 40%,
60%, 80% and 100% of the power rate of the ultrasonic probe (40, 80, 120, 160 and 200 W). The results are shown in Table 2. The
intensity of sonication is proportional to the amplitude of vibration will lead to an increase in the intensity of vibration and to an
increase in the sonochemical effects. Increasing the ultrasound power intensity up to 80% induces relatively higher yields ad shorter
reaction times, beyond this level, the yield decrease slightly. Generally, the increase in the acoustic power could increase the number of
active cavitation bubbles. Both increases can be expected to result in an increase in the maximum collapse temperature [23], and the
respective reaction could be accelerated. The results are summarized in Table 2. It can easily be seen that the condensation of a series
of monochloroacetic acid, ammonium thiocyanate, and 4-chlorobenzaldehyde in H2O/TFE (1:1) under ultrasound leads to novel
biologically important 5,5'-(4-chlorophenylmethylene)bis(4-hydroxythiazole-2(3H)-one) (4g).
In the next step the scope and efficiency of the process was explored under the optimized conditions. For this purpose,
monochloroacetic acid (2 mmol), ammonium thiocyanate (2 mmol) and a broad range of structurally diverse aromatic aldehydes (1
mmol) were condensed in the presence of ultrasonic irradiation at room temperature to achieve the desired product, and the results are
displayed in Table 3. As shown in Table 3, products were obtained in excellent yields. It was found that aromatic aldehydes both with
electron withdrawing and donating groups in reaction with other starting materials have excellent isolated yield.
The formation of compounds 4a-o could be explained by the reaction sequence in Fig. 1. On the basis of this mechanism, first, a
condensation of monochloroacetic acid 2 with ammonium thiocyanate 3 is proposed to give the intermediate A to C and D. Then, the
intermediate E is likely formed via condensation of aromatic aldehyde 1a-o with D which is tautomer of C. The next step is Michael
addition of another intermediate of F to yield adduct G. Finally, after the tautomeric proton shift, the desired product 4a-o is formed
(Fig. 1).
3. Conclusion
In summary, we have found an efficient and practical procedure for the synthesis of 5,5'-(arylmethylene)bis(4-hydroxythiazole-2(3H)-one)
via condensation monochloroacetic acid, ammonium thiocyanate, and aromatic aldehyde in an aqueous fluoroalcohol solvent system under
ultrasound irradiation at room temperature.
4. Experimental
4.1 Reagents and equipment
1
Products were characterized by comparison with authentic samples and by spectroscopy data (IR, H NMR and 13C NMR spectra). The
NMR spectra were recorded on a Bruker Avance DEX500 MHz instrument. The spectra were measured in DMSO-d6 relative to TMS as the
internal standard. Melting points were determined using Barnstead-Electro thermal 9300 Melting Points. Mass spectra were recorded on a VG
micromass 7070H and Finnigan mat 1020B mass spectrometers operating at 70 eV. Elemental analyses were performed on Yanco-CHN
CORDER elementary analyzer. IR spectra were recorded on a Perkin-Elmer 781 spectrophotometer from KBr pelletes. All reagents were
purchased from Merck and Aldrich and were used without further purification. Analytical TLC was performed on DC-Alufolien Silica gel
60F254 Merck. All yields refer to isolated products after purification. All sonochemical reactions were carried out in a thermostated (25 ± 1 oC)
ultrasonic cleaning bath at 40 kHz. The ultrasonic cleaner had an output power of 200 W. The tank dimensions were 290 × 240 × 150 mm with
a liquid (water) holding capacity of 9.5 L. The reactions were carried out in a RB flask of 10 mL capacity, suspended at the center of the
cleaning bath, 5 cm below the surface of the liquid.
4.2 Typical experimental procedure
A mixture of monochloroacetic acid (2 mmol), ammonium thiocyanate (2 mmol) and 4-chlorobenzaldehyde (1 mmol) were stirred in one-
pot in H2O/TFE (1:1) (5 mL) at refluxing temperature and ultrasound irradiation at room temperature for appropriate time (Table 3). The
ultrasonic apparatus used to show the temperature automatically so the temperature was controlled and fixed at room temperature by pouring

cold water in the bath in the case of any elevation of temperature. The progress of the reaction is monitored by TLC. After completion of the
reaction, the corresponding solid product was obtained through simple filtering, and recrystallized from ethanol affording the highly pure
products (4a-m).
o
5,5'-(Phenylmethylene)bis(4-hydroxythiazole-2(3H)-one) (4a): 0.341 g (96%), pale yellow solid, mp: 182-184 C. IR (KBr, cm-1): 3556-
1
3233 (br.), 3098, 2987, 1698, 1530, 1443, 712. H NMR (500 MHz, DMSO-d6): δ 3.54 (s, 1H, CH), 7-8 (m, 5H, Ar-H), 8.32 (s, 2H, NH),
10.14 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 77.9, 125.7, 127.8, 128.9, 129.6, 132.6, 136.8, 140.9, 142.8, 143.7, 146.8, 176.9, 196.5.
MS (EI) m/z (%): 322 (M+, 80), 245 (15). HRMS (EI) Found: 322.0303 M+, calcd. 322.0103 M+. Anal. Calcd. for C13H10N2O4S2: C, 48.44; H,
3.13; N, 8.69; S, 19.89. Found: C, 48.047; H, 3.15; N, 8.63; S, 19.90.
o
5,5'-(p-Tolylmethylene)bis(4-hydroxythiazole-2(3H)-one) (4b): 0.342 g (93%), yellow solid, mp: 195-197 C. IR (KBr, cm-1): 3543-3223
1
(br.), 3088, 2987, 2876, 1689, 1523, 1423, 732. H NMR (500 MHz, DMSO-d6): δ 1.95 (s, 3H, CH3), 5.20 (s, 1H, CH), 7-8 (m, 5H, Ar-H),
8.43 (s, 2H, NH), 12.06 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 17.45, 44.47, 122.7, 124.7, 128.2, 135.9, 139.7, 141.5, 146.7, 149.8,
151.6, 167.9, 176.2, 196.9. MS (EI) m/z (%): 336 (M+, 56), 244 (35). HRMS (EI) Found: 336.006 M+, calcd. 336.0204 M+. Anal. Calcd. for
C14H12N2O4S2: C, 49.99; H, 3.60; N, 8.33; S, 19.06. Found: C, 49.97; H, 3.61; N, 8.32; S, 19.08.
5,5'-((4-Nitrophenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4c): 0.391 g (98%), yellow solid, mp: 211-213 oC. IR (KBr, cm-1): 3621-
1
3265 (br.), 3102, 2899, 1693, 1522, 1465, 1342, 741. H NMR (500 MHz, DMSO-d6): δ 4.76 (s, 1H, CH), 7.49 (d, 2H, J = 7.5 Hz), 8.12 (d,
2H, J = 7.5 Hz), 8.09 (s, 2H, NH), 11.76 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 70.7, 121.8, 124.8, 125.8, 126.8, 128.7, 132.8, 142.8,
144.9, 149.0, 170.8, 175.9, 196.8. MS (EI) m/z (%) 367 (M+, 47), 244 (15). HRMS (EI) Found: 399.4903 M+, calcd. 366.9902 M+. Anal. Calcd.
for C13H9N3O6S: C, 42.50; H, 2.47; N, 11.44; S, 17.46. Found: C, 42.52; H, 2.48; N, 11.45; S, 17.48.
5,5'-((3-Nitrophenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4d): 0.391 g (98%), pale yellow solid, mp: 203-205 oC. IR (KBr, cm-1):
3601-3232 (br.), 3094, 2934, 1656, 1557, 1445, 1339, 708. 1H NMR (500 MHz, DMSO-d6): δ 4.97 (s, 1H, CH), 7.49-8.11 (m, 4H, Ar-H), 8.11
(s, 2H, NH), 12.86 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 69.6, 126.8, 128.8, 146.6, 148.3, 144.8, 151.9, 152.7, 155.9, 165.8, 170.9,
175.0, 199.2. MS (EI) m/z (%) 367 (M+, 57), 244 (27). HRMS (EI) Found: 399.4903 M+, calcd. 366.9902 M+. Anal. Calcd. for C13H9N3O6S:
C, 42.50; H, 2.47; N, 11.44; S, 17.46. Found: C, 42.52; H, 2.48; N, 11.45; S, 17.48.
o
5,5'-((2-Chlorophenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4e): 0.376 g (97%), yellow solid, mp: 231-233 C. IR (KBr, cm-1):
1
3621-3165 (br.), 3096, 2812, 1683, 1520, 1456 1309, 7031. H NMR (500 MHz, DMSO-d6): δ 4.29 (s, 1H, CH), 7.20-7.87 (m, 4H, Ar-H),
8.61 (s, 2H, NH), 11.13 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 77.9, 125.7, 127.8, 128.9, 129.7, 129.9, 132.7, 135.8, 141.8, 144.7,
174.7, 175.9, 194.9. MS (EI) m/z (%) 356 (M+, 19), 244 (16). HRMS (EI) Found: 355.9703 M+, calcd. 355.9704 M+. Anal. Calcd. for
C13H9ClN2O4S2: C, 43.76; H, 2.54; N, 17.94; S, 17.97. Found: C, 43.74; H, 2.55; N, 17.96; S, 17.99.
o
5,5'-((3-Chlorophenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4f): 0.368 g (95%), white solid, mp: 241-243 C. IR (KBr, cm-1):
1
3601-3112 (br.), 3089, 2821, 1690, 1565, 1485, 1328, 711. H NMR (500 MHz, DMSO-d6): δ 8.14 (s, 2H, NH), 4.62 (s, 1H, CH), 7.32-8.10
(m, 4H, Ar-H), 8.14 (s, 2H, NH), 11.76 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 76.9, 122.8, 123.8, 127.8, 130.6, 134.8, 141.9, 143.8,
145.9, 150.9, 151.0, 170.8, 196.5. MS (EI), m/z (%) 356 (M+, 32), 244 (21). HRMS (EI) Found: 355.9703 M+, calcd. 355.9704 M+. Anal.
Calcd. for C13H9ClN2O4S2: C, 43.76; H, 2.54; N, 17.94; S, 17.97. Found: C, 43.74; H, 2.55; N, 17.96; S, 17.99.
5,5'-((4-Chlorophenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4g): 0.383 g (96%), pale yellow solid, mp: 251-253 oC. IR (KBr, cm-
1
1): 3565-3167 (br.), 3088, 2805, 1663, 1512, 1433, 1323, 721. H NMR (500 MHz, DMSO-d6): δ 4.56 (s, 1H, CH), 7.18 (d, 2H, J = 7.5 Hz),
7.65 (d, 2H, J = 7.5 Hz), 8.41 (s, 2H, NH), 12.83 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 74.8, 129.2, 130.8, 131.6, 134.9, 141.8,
142.4, 143.6, 147.8, 150.8, 172.8, 175.2, 197.2. (EI) m/z (%)356 (M+, 43), 244 (28). HRMS (EI) Found: 355.9703 M+, calcd. 355.9704 M+.
Anal. Calcd. for C13H9ClN2O4S2: C, 43.76; H, 2.54; N, 17.94; S, 17.97. Found: C, 43.74; H, 2.55; N, 17.96; S, 17.99.
5,5'-((2,4-Dichlorophenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4h): 0.406 g (96%), yellow solid, mp: 238-240 oC. IR (KBr, cm-1):
3683-3111 (br.), 3079, 2834, 1676, 1555, 1459, 1389, 741. 1H NMR (500 MHz, DMSO-d6): δ 4.78 (s, 1H, CH), 7.15 (d, 1H, J = 7.5 Hz), 7.31
(d, J = 7.5 Hz, 1H), 7.65 (d, 2H, J = 7.5 Hz), 8.32 (s, 2H, NH), 11.80 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 69.8, 128.8, 130.7,
132.6, 134.8, 157.8, 140.8, 141.8, 146.8, 151.6, 171.8, 178.9, 198.5. MS (EI), m/z (%) 391 (M+, 30), 244 (16). HRMS (EI) Found: 389.9306
M+, calcd. 389.9304 M+. Anal. Calcd. for C13H8Cl2N2O4S2: C, 39.91; H, 2.06; N, 7.16; S, 16.39. Found: C, 39.93; H, 2.03; N, 7.15; S, 16.40.
o
5,5'-((4-Flouro-4-fluorophenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4i): 0.364 g (98%), pale yellow solid, mp: 237-239 C. IR
1
(KBr, cm-1): 3620-3094 (br.), 3065, 2865, 1676, 1512, 1424, 1354, 731. H NMR (500 MHz, DMSO-d6): δ 4.25 (s, 1H, CH), 7.11 (d, 2H,
J=7.5 Hz), 7.65 (d, 2H, J = 7.5 Hz), 8.18 (s, 2H, NH), 12.01 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 72.9, 118.2, 123.7, 127.9, 131.8,
132.9, 133.6, 137.9, 159.2, 161.8, 171.0, 175.2, 198.8. 19F NMR (470 MHz, DMSO-d6): δ 73.44 (s, 1F); MS (EI) m/z (%) 340 (M+, 18), 244
(15). HRMS (EI) Found: 340.0002 M+, calcd. 340.0001 M+. Anal. Calcd. for C13H9FN2O4S2: C, 45.88; H, 2.67; N, 8.23; S, 18.84. Found: C,
45.86; H, 2.66; N, 8.25; S, 18.46.
5,5'-((4-Bromophenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4j): 0.407 g (94%), brown solid, mp: 207-209oC. IR (KBr, cm-1):
3643-3154 (br.), 3101, 2843, 1676, 1520, 1498, 1376, 711. 1H NMR (500 MHz, DMSO-d6): δ 4.16 (s, 1H, CH), 7.43 (d, 2H, J=7.5 Hz), 7.89
(d, 2H, J = 7.5 Hz), 8.14 (s, 2H, NH), 12.13 (s, 2H, OH). 13C NMR (DMSO-d6, 125 MHz): δ 74.8, 120.8, 133.8, 134.9, 135.8, 141.8, 146.8,
147.9, 150.9, 152.9, 170.9, 175.9, 198.9. MS (EI) m/z (%) 401 (M+, 64), 244 (7). HRMS (EI) Found: 399.9201 M+, calcd. 399.9202 M+. Anal.
Calcd. for C13H9BrN2O4S2: C, 38.91; H, 2.26; N, 6.98; S, 15.98. Found: C, 38.92; H, 2.23; N, 6.96; S, 15.95
5,5'-((4-hydroxyphenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4k): 0.325 g (88%), pale yellow solid, mp: 214-216 oC. IR (KBr, cm-
1
1): 3601-3111 (br.), 3069, 2832, 1675, 1541, 1487, 1365, 710. H NMR (500 MHz, DMSO-d6): δ 4.18 (s, 1H, CH), 6.81 (d, 2H, J = 7.8 Hz),
7.18 (d, 2H, J = 7.8 Hz), 9.31 (s, 1H, OH), 8.22 (s, 2H, NH), 12.23 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 75.9, 118.9, 121.2, 131.4,

136.9, 139.9, 141.9, 148.9, 156.4, 157.9, 172.9, 177.2, 199.3. MS (EI) m/z (%) 338 (M+, 12), 244 (15) HRMS (EI) Found: 338.0004 M+, calcd.
338.0002 M+. Anal. Calcd. for C13H10N2O5S2: C, 46.15; H, 2.98; N, 8.28; S, 18.95. Found: C, 46.13; H, 2.99; N, 8.27; S, 18.94.
o
5,5'-((4-Methoxyphenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4l): 0.364 g (95%), yellow solid, mp: 227-229 C. IR (KBr, cm-1):
1
3698-3119 (br.), 31018, 2827, 1660, 1554, 1487, 1367, 730. H NMR (500 MHz, DMSO-d6): δ 3.87 (s, 3H, CH3), 4.82 (s, 1H, CH), 6.89 (d,
2H, J = 7.5 Hz), 7.23 (d, 2H, J = 7.5 Hz), 8.31 (s, 2H, NH), 12.91 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 45.9, 67.3, 121.8, 130.2,
132.9, 134.5, 137.9, 139.9, 143.6, 147.9, 159.8, 160.9, 170.9, 177.2, 198.1. MS (EI) m/z (%) 352 (M+, 17), 244 (14) HRMS (EI) Found:
352.0303 M+, calcd. 352.0202 M+. Anal. Calcd. for C14H12N2O6S2: C, 47.72; H, 3.43; N, 7.95; O, 22.70; S, 18.20. Found: C, 43.71; H, 3.44;
N, 7.396; S, 18.22.
5,5'-((2,4-Dimethoxyphenyl)methylene)bis(4-hydroxythiazole-2(3H)-one) (4m): 0.393 g (95%), yellow solid, mp: 271-273 oC. IR (KBr, cm-
1): 3504-3133 (br.), 3069, 2817, 1619, 1523, 1463, 1354, 732. 1H NMR (500 MHz, DMSO-d6): δ 3.94 (s, 6H, 2×CH3), 4.54 (s, 1H, CH), 6.78
(d, 2H, J = 7.7 Hz), 7.85 (s, 2H, Ar-H), 8.09 (d, 1H, J = 7.7 Hz, Ar-H), 8.15 (s, 2H, NH), 12.63 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6):
δ 21.9, 55.9, 67.8, 121.9, 122.8, 123.8, 134.9, 136.8, 139.8, 159.2, 159.6, 170.8, 178.9, 199.9. MS (EI) m/z (%) 382 (M+, 37), 244 (18). HRMS
(EI) Found: 382.0303 M+, calcd. 382.0302 M+. Anal. Calcd. for C15H14N2O6S2: C, 47.11; H, 3.69; N, 7.33; S, 16.77. Found: C, 47.12; H, 3.70;
N, 7.35; S, 16.72.
5,5'-(Naphthalen-2-ylmethylene)bis(4-hydroxythiazole-2(3H)-one) (4n): 0.363 g (90%), pale yellow solid, mp: 188-200 oC. IR (KBr, cm-1):
3678-3098 (br.), 3076, 2843, 1663, 1502, 1433, 1343, 711. 1H NMR (500 MHz, DMSO-d6): δ 4.85 (s, 1H, CH), 7.19-8.03 (m, 7H, Ar-H), 8.11
(s, 2H, NH), 12.10 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 84.9, 121.8, 125.9, 126.9, 127.0, 127.2, 127.6, 128.9, 131.9, 134.8, 135.8,
137.8, 138.9, 143.8, 171.9, 176.8, 196.7. MS (EI) m/z (%) 372 (M+, 35), 244 (21). HRMS (EI) Found: 372.0202 M+, calcd. M+, 372.0201.
Anal. Calcd. for C17H12N2O2S2: C, 54.83; H, 3.25; N, 7.52; S, 17.22. Found: C, 50.82; H, 3.26; N, 7.53; S, 17.24.
5,5'-(Pyridin-4-ylmethylene)bis(4-hydroxythiazole-2(3H)-one) (4o): 0.323 g (91%), pale yellow solid, mp: 255-257oC. IR (KBr, cm-1):
3532-3107 (br.), 3099, 2825, 1653, 1502, 1463, 1343, 711. 1H NMR (500 MHz, DMSO-d6): δ 4.45 (s, 1H, CH), 7.33 (d, 2H, J = 7.8 Hz), 7.75
(d, 2H, J = 7.5 Hz), 8.47 (s, 2H, NH), 11.87 (s, 2H, OH). 13C NMR (125 MHz, DMSO-d6): δ 67.7, 121.8, 124.8, 149.7, 150.7, 151.7, 152.8,
152.8, 153.7, 170.6, 175.9, 198.9. MS (EI) m/z (%) 323 (M+, 27), 244 (35). HRMS (EI) Found: 323.0001 M+, calcd. 323.0002 M+. Anal. Calcd.
for C12H9N3O4S2: C, 44.57; H, 2.81; N, 13.00; S, 19.83. Found: C, 40455; H, 2.83; N, 13.02; S, 19.82.
Acknowledgments
We are grateful the research council of Payame Noor University.
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Fig 1. Proposed mechanism for the syntheis of 4a-o in in fluoro alcohols under ultrasound irradiation at r.t.

Scheme 1. One-pot pseudo five-component Synthesis of 5’-(chlorophenyle)bis(4-hydroxythiazole-2(3H)-one).

Table 1
Synthesis of (4g) in different solvents under with/without ultrasound irradiation.
Entry
Solvent
With sonicationa
Time (min)
Without sonicationb
Time (min)
Yield (%)c
Yield (%)c
1
2
3
4
5
6
7
8
MeOH
EtOH
THF
DCM
Acetonitrile
DMSO
DMF
Water
1,4-Dioxane
Neat
25
25
55
60
60
65
65
25
70
50
50
20
20
15
15
10
10
5
70
70
45
50
55
50
55
65
45
8
130
130
150
170
170
155
160
140
170
100
80
95
95
85
70
65
65
50
60
60
50
45
50
45
50
60
40
5
10
72
75
75
80
85
85
90
9
10
11
12
13
14
15
16
17
18
Neat
15d
75
80
80
85
90
90
96
H2O/EtOH (3:1)
H2O/EtOH (1:3)
H2O/EtOH (1:1)
TFE
H2O/TFE (3:1)
H2O/TFE (1:3)
H2O/TFE (1:1)
a The reaction was carried conducted with monochloroacetic acid, (2 mmol), ammonium thiocyanate (2 mmol) and 4-chlorobenzaldehyde (1
mmol) under ultrasonic frequencies of 40 kHz, the ultrasonic power was kept at 160 W.
b Monochloroacetic acid (2 mmol), ammonium thiocyanate (2 mmol) and 4-chlorobenzaldehyde (1 mmol) at refluxing temperature with high
stirring condition.
c Isolated yield.
d The temperature is 110 oC.

Table 2
Effect of ultrasound intensity power on the synthesis of 4g.a
Entry
%Max power Time (min)
Yield (%)b
intensity (W)
1
2
3
4
5
20% (40)
40% (80)
60% (120)
80% (160)
100% (200)
20
15
10
8
90
92
95
96
95
8
a The reaction was carried with monochloroacetic acid (2 mmol), ammonium thiocyanate (2 mmol) and 4-chlorobenzaldehyde (1
mmol) in H2O/TFE (1:1) under ultrasound irradiation at r.t.
b Isolated yield.

Table 3
Pesudo five-component synthesis of 4a-o in H2O/TFE (1:1) under ultrasound irradiation at r.t. a
Entry
Ar
Time
(min)
5
10
5
5
5
5
5
5
5
5
10
5
5
15
10
Product
Yields
(%)b
96
93
98
98
97
95
96
96
98
94
88
95
95
90
91
Mp (oC)
1
2
3
4
5
6
7
8
C6H5
182-184
195-197
211-213
203-205
231-233
241-243
251-253
238-240
237-239
207-209
214-216
227-229
271-273
188-200
255-257
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4-CH3C6H4
4-NO2C6H4
3-NO2C6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
2,4-Cl2C6H3
4-FC6H4
4-BrC6H4
4-OHC6H4
4-CH3OC6H4
2,4-(CH3O)C6H3
2-Naphthyl
4-Pyridinyl
9
10
11
12
13
15
14
a Reaction conditions: monochloroacetic acid, ammonium thiocyanate and arylaldehyde (2:2:1, molar ratio) in H2O/TFE (1:1) under ultrasound
irradiation (power intensity up to 80% at r.t.).
b Isolated yield.