Green approach: An efficient synthesis of 2,4-disubstituted-1,3-thiazoles and selenazoles in aqueous medium under ultrasonic irradiation

Article abstract of DOI:10.1007/s11164-014-1879-z

An efficient and rapid procedure for the synthesis of 2,4-disubstituted-1,3-thiazoles and selenazoles has been described by the reaction of α-bromoketones with thiourea, phenylthiourea and selenourea at ambient temperature in aqueous medium under ultrasonic irradiation. Analytically pure products were formed within 10-60 s in excellent yields. The advantageous features of this non-conventional methodology over conventional methods are the operational simplicity, easy handling, yield-enhancing, time-reducing, mild reaction conditions and no by-product production.

Full text of DOI:10.1007/s11164-014-1879-z

Res Chem Intermed
DOI 10.1007/s11164-014-1879-z
Green approach: an efficient synthesis of
2,4-disubstituted-1,3-thiazoles and selenazoles
in aqueous medium under ultrasonic irradiation
•
Gondru Ramesh Banothu Janardhan
Bavantula Rajitha
•
Received: 12 October 2014 / Accepted: 16 November 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract An efficient and rapid procedure for the synthesis of 2,4-disubstituted-
1,3-thiazoles and selenazoles has been described by the reaction of a-bromoketones
with thiourea, phenylthiourea and selenourea at ambient temperature in aqueous
medium under ultrasonic irradiation. Analytically pure products were formed within
10–60 s in excellent yields. The advantageous features of this non-conventional
methodology over conventional methods are the operational simplicity, easy han-
dling, yield-enhancing, time-reducing, mild reaction conditions and no by-product
production.
Keywords Cavitation effect ꢀ Green chemistry ꢀ Thiazoles ꢀ Selenazoles ꢀ
Ultrasonication
Introduction
The applications of green chemistry principles have led to the development of
cleaner and environmentally benign chemical processes. In recent years, ultrasound
irradiation has been extensively applied in organic reactions because of its special
sonochemical property such as the cavitation effect that accelerates both catalytic
and non-catalytic synthetic reactions [1]. More energy consumption for heating and
production of hazardous by-products are some disadvantageous factors of normal
conventional techniques, which show adverse effects on the environment.
Electronic supplementary material The online version of this article (doi:10.1007/s11164-014-1879-z)
contains supplementary material, which is available to authorized users.
G. Ramesh ꢀ B. Janardhan (&) ꢀ B. Rajitha
Department of Chemistry, National Institute of Technology, Warangal 506004, Telangana State,
India
e-mail: janardhan.nitw@gmail.com
123

G. Ramesh et al.
Moreover, when compared to the classical thermal methods of chemical processes,
an ultrasonic irradiation method has been attracting the modern synthetic chemists
due to its advantageous features, i.e., decreasing reaction times, increasing yields [2,
3], easy workup procedures, avoiding harsh reaction conditions [4], better
selectivity and high conversions [5].
The thiazole ring is a core structural backbone of various natural and synthetic
pharmacologically active compounds such as vitamin B1 (thiamine), penicillin,
meloxicam, fanetizole and cefdinir. Thiazole derivatives have diverse applica-
tions in various fields of chemistry including medicinal and agricultural, such as
anticancer [6], antitumor [7], antimalarial [8], anti-inflammatory [9], antimicro-
bial [10], antihypertensive [11], antiparasitic [12], HIV-1 reverse transcriptase
inhibitors [13] and herbicidal properties [14]. They have also been reported as
ligands at estrogen receptors [15] and novel class adenosine receptor antagonists
[16], and used as organic functional materials such as fluorescent dyes [17] and
liquid crystals [18], and also acting as good pharmacophores for the design of
bioactive molecules such as the bioisoster of the imidazole ring [19]. Similarly,
selenazoles have also been reported to possess antibacterial [20], antifilarial,
antitumor [21], superoxide anion scavenging [22] properties and to act as Akt,
mitogen protein kinase activator [23], and heavy metal detoxifying agents [24].
The structures of fanetizole, cefdinir and selenazofurin, and their pharmacological
activities are given in Fig. 1.
In view of the importance of thiazole and selenazole derivatives in various fields
of chemistry, the classical Hantzsch synthesis as well as several methodologies have
been reported utilizing various catalytic systems such as ammonium-12-molybdo-
phosphate [25], b-cyclodextrin [26], NaCl [27], HMCM-41 [28], iodine [29], TiO2
[30], CuPy2Cl2 [31], graphite oxide [32] and silica chloride [33], and also reported
in different solvent systems, such as ionic liquids [34], PEG-400 [35], glycerin [36],
and water [37]. However, most of these reported methods have one or several
drawbacks such as lower yields, longer reaction times, complicated isolation
procedures and the use of hazardous and expensive catalysts making them
environmentally unfriendly. To overcome the above limitations, and as a part of our
endeavor towards the development of novel eco-friendly methodologies for the
synthesis of biologically potent heterocyclic compounds [38], we propose here a
versatile, simple, mild, environmentally benign and highly efficient protocol for the
synthesis of 2,4-disubstituted-1,3-thiazoles and 1,3-selenazoles in aqueous medium
under ultrasonic irradiation.
O
H
O
NH2
N
H
N
H
N
H H
N
N
S
N
N
O
H2N
e
S
H
O
S
O
S
O
H
O
H
O
H
COO
Fanetizole (antiinflammatory)
Cefdinir (bacteriocidal antibiotic)
Selenazofurin (antibacterial)
Fig. 1 Biologically active thiazole and selenazole derivatives
123

Green approach
Experimental
Materials and methods
All the reagents and solvents were purchased from Aldrich/Merck and used without
further purifications. Melting points were determined in open capillaries with Stuart
SMP30 melting point apparatus and are uncorrected. The progress of the reactions
as well as the purity of the compounds was checked using F254 silica-gel precoated
TLC sheets (Merck, Mumbai, India) using hexane/ethyl acetate (8:2) as eluent, and
the developed chromatogram was visualized under UV light and iodine vapors. IR
spectra were recorded on a Perkin–Elmer 100S spectrophotometer (Perkin-Elmer,
1
UK). H NMR spectra were obtained on Bruker (400 MHz) spectrometer (Bruker,
Germany) using TMS as internal standard. Elemental analyses were performed on a
Carlo-Erba model EA1108 analytical unit (Triad, New Jersey, USA) and the values
are 0.4 % of theoretical values. Mass spectra were recorded on a Jeol JMSD-300
spectrometer (Jeol, Tokyo, Japan). Sonication was performed on PCi-Analytics-
6.5L200H1DTC ultrasonic cleaner (PCi-Analytics, 25 and 50 kHz, input voltage
range of 170–270 V AC, 50 Hz) (Mumbai, India).
General procedure for the synthesis of 2,4-disubstituted-1,3-thiazoles
and selenazoles (3–16)
A 100-mL borosil test-tube was charged with phenacyl bromide (1a–h)/3(2-
bromoacetyl)coumarin (1i–n) (1 mmol), thiourea (2a)/phenylthiourea (2b)/selenou-
rea (2c) (1 mmol) and water (1 mL). The tube was kept in such a way that the
surface of the reactants is just lower than the water level of the ultrasonic bath in
which they were sonicated with a frequency of 50 kHz at 25 °C for about 10–60 s.
The progress of the reaction was monitored by TLC. After completion of the
reaction, the solid separated out was filtered and washed with water. Analytically
pure products were obtained without further recrystallization.
Spectral data of newly synthesized compounds
4-(4-Fluorophenyl)-1,3-selenazol-2-amine (4c)
White solid; IR (KBr, mmax, cm-1): 3,392, 3,261 (NH2), 1,628 (C=N), 1,098 (C–F);
1H NMR (400 MHz, DMSO-d6): d (ppm) 7.19 (s, 1H), 7.28 (s, 1H), 7.32 (d,
J = 8.0 Hz, 1H), 7.77–7.81 (m, 3H), 8.44 (s, 1H); MS (ESI) m/z: 242 [M ? H]?;
Anal. calcd. for C9H7FN2Se: C, 44.83; H, 2.93; N, 11.62. Found: C, 44.61; H, 3.17;
N, 11.83.
4-([1,10-Biphenyl]-4-yl)thiazol-2-amine (10a)
1
White solid; IR (KBr, mmax, cm-1): 3,370, 3,258 (NH2), 1,625 (C=N); H NMR
(400 MHz, DMSO-d6): d (ppm) 7.27 (s, 1H), 7.39 (t, J = 7.6 Hz, 1H), 7.49 (t,
J = 7.2 Hz, 2H), 7.73 (d, J = 7.2 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.84 (d,
123

G. Ramesh et al.
J = 8.4 Hz, 2H), 8.48 (s, 2H); MS (ESI) m/z: 253 [M ? H]?; Anal. calcd. for
C15H12N2S: C, 71.40; H, 4.79; N, 11.10. Found: C, 71.16; H, 4.54; N, 11.25.
4-([1,10-Biphenyl]-4-yl)-N-phenylthiazol-2-amine (10b)
White solid; IR (KBr, mmax, cm-1): 3,332 (NH), 1,698 (C=N); 1H NMR (400 MHz,
DMSO-d6): d (ppm) 6.99 (t, J = 7.2 Hz, 1H), 7.31–7.43 (m, 6H), 7.61–7.69 (m,
6H), 7.93 (d, J = 8.4 Hz, 2H), 10.47 (s, 1H); MS (ESI) m/z: 329 [M ? H]?; Anal.
calcd. for C21H16N2S: C, 76.80; H, 4.91; N, 8.53. Found: C, 76.57; H, 4.70; N, 8.27.
4-([1,10-Biphenyl]-4-yl)-1,3-selenazol-2-amine (10c)
1
White solid; IR (KBr, mmax, cm-1): 3,490, 3,240 (NH2), 1,613 (C=N); H NMR
(400 MHz, DMSO-d6): d (ppm) 7.38–7.42 (m, 1H), 7.50 (t, J = 7.2 Hz, 2H), 7.55
(s, 1H), 7.73–7.80 (m, 6H), 9.02 (s, 2H); MS (ESI) m/z: 300 [M ? H]?; Anal. calcd.
for C15H12N2Se: C, 60.21; H, 4.04; N, 9.36. Found: C, 60.56; H, 4.34; N, 9.12.
3-(2-Aminothiazol-4-yl)-6-chloro-2H-chromen-2-one (12a)
Yellow solid; IR (KBr, mmax, cm-1): 3,315, 3,248 (NH2), 1,735 (C=O), 1,631
(C=N), 789 (C–Cl); 1H NMR (400 MHz, DMSO-d6): d (ppm) 7.77 (d, J = 7.2 Hz,
1H), 7.93 (d, J = 7.6 Hz, 1H), 8.08 (s, 1H), 8.45 (s, 1H), 8.61 (s, 1H), 8.80 (s, 2H);
MS (ESI) m/z: 279 [M ? H]?; Anal. calcd. for C12H7ClN2O2S: C, 51.71; H, 2.53,
N, 10.05. Found: C, 51.42; H, 2.75; N, 10.37.
6-Chloro-3-(2-(phenylamino)thiazol-4-yl)-2H-chromen-2-one (12b)
Yellow solid, IR (KBr, mmax, cm-1): 3,359 (NH), 1,719 (C=O), 1,607 (C=N), 745
(C–Cl); 1H NMR (400 MHz, DMSO-d6): d (ppm) 7.01 (t, J = 7.2 Hz, 1H), 7.38 (t,
J = 8.0 Hz, 2H), 7.48 (d, J = 8.8 Hz, 1H), 7.62–7.65 (m, 1H), 7.76 (d, J = 8.0 Hz,
2H), 7.80 (s, 1H), 8.13 (s, 1H), 8.66 (s, 1H), 10.36 (s, 1H); MS (ESI) m/z: 355
[M ? H]?; Anal. calcd. for C18H11ClN2O2S: C, 60.93; H, 3.12; N, 7.90. Found: C,
60.75; H, 3.28; N, 7.72.
3-(2-Amino-1,3-selenazol-4-yl)-6-chloro-2H-chromen-2-one (12c)
Yellow solid; IR (KBr, mmax, cm-1): 3,297, 3,441 (NH2), 1,728 (C=O), 1,625
(C=N), 785 (C–Cl); 1H NMR (400 MHz, DMSO-d6): d (ppm) 7.89 (d, J = 6.8 Hz,
1H), 7.92 (d, J = 7.2 Hz, 1H), 8.09 (s, 1H), 8.46 (s, 1H), 8.61 (s, 1H), 8.79 (s, 2H);
MS (ESI) m/z: 325 [M]?; Anal. calcd. for C12H7ClN2O2Se: C, 44.26; H, 2.17; N,
8.60. Found: C, 44.55; H, 2.32; N, 8.36.
3-(2-Aminothiazol-4-yl)-6-bromo-2H-chromen-2-one (13a)
Yellow solid; IR (KBr, mmax, cm-1): 3,340, 3,186 (NH2), 1,717 (C=O), 1,602
(C=N), 602 (C–Br); 1H NMR (400 MHz, DMSO-d6): d (ppm) 7.19 (s, 2H), 7.40 (d,
123

Green approach
J = 8.8 Hz, 1H), 7.54 (s, 1H), 7.72–7.75 (m, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.44 (s,
1H); MS (ESI) m/z: 324 [M ? H]?; Anal. calcd. for C12H7BrN2O2S: C, 44.60; H,
2.18; N, 8.67. Found: C, 44.45; H, 2.37; N, 8.46.
6-Bromo-3-(2-(phenylamino)thiazol-4-yl)-2H-chromen-2-one (13b)
Yellow solid; IR (KBr, mmax, cm-1): 3,358 (NH), 1,719 (C=O), 1,605 (C=N), 558
(C–Br); 1H NMR (400 MHz, DMSO-d6): d (ppm) 7.01 (t, J = 7.6 Hz, 1H),
7.37–7.44 (m, 3H), 7.75–7.81 (m, 4H), 8.28 (d, J = 7.6 Hz, 1H), 8.67 (s, 1H), 10.36
(s, 1H); MS (ESI) m/z: 400 [M ? H]?; Anal. calcd. for C18H11BrN2O2S: C, 54.15;
H, 2.78; N, 7.02. Found: C, 54.36; H, 2.56; N, 7.22.
3-(2-Amino-1,3-selenazol-4-yl)-6-bromo-2H-chromen-2-one (13c)
Yellow solid; IR (KBr, mmax, cm-1): 3,483, 3,372 (NH2), 1,735 (C=O), 1,620
(C=N), 587 (C–Br); 1H NMR (400 MHz, DMSO-d6): d (ppm) 7.94 (d, J = 8.0 Hz,
1H), 8.03 (d, J = 7.2 Hz, 1H), 8.26 (s, 1H), 8.44 (s, 1H), 8.52 (s, 2H), 8.95 (s, 1H);
MS (ESI) m/z: 371 [M ? H]?; Anal. calcd. for C12H7BrN2O2Se: C, 38.95; H, 1.91;
N, 7.57. Found: C, 38.65; H, 1.67; N, 7.84.
3-(2-Aminothiazol-4-yl)-6,8-dibromo-2H-chromen-2-one (14a)
Yellow solid; IR (KBr, mmax, cm-1): 3,492, 3,389 (NH2), 1,740 (C=O), 1,692
1
(C=N), 593, 608 (C–Br); H NMR (400 MHz, DMSO-d6): d (ppm) 7.23 (s, 2H),
7.56 (s, 1H), 8.09–8.14 (m, 2H), 8.41 (s, 1H); MS (ESI) m/z: 403 [M ? H]?; Anal.
calcd. for C12H6Br2N2O2S: C, 35.85; H, 1.50; N, 6.97. Found: C, 35.97; H, 1.39; N,
7.21.
6,8-Dibromo-3-(2-(phenylamino)thiazol-4-yl)-2H-chromen-2-one (14b)
Yellow solid; IR (KBr, mmax, cm-1): 3,362 (NH), 1,728 (C=O), 1,603 (C=N), 501,
1
562 (C–Br); H NMR (400 MHz, DMSO-d6): d (ppm) 7.01 (t, J = 7.2 Hz, 1H),
7.38 (t, J = 8.0 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), 7.82 (s, 1H), 8.12 (s, 1H), 8.32
(s, 1H), 8.64 (s, 1H), 10.37 (s, 1H); MS (ESI) m/z: 479 [M ? H]?; Anal. calcd. for
C18H10Br2N2O2S: C, 45.21; H, 2.11; N, 5.86. Found: C, 45.43; H, 2.02; N, 5.67.
3-(2-Amino-1,3-selenazol-4-yl)-6,8-dibromo-2H-chromen-2-one (14c)
Yellow solid; IR (KBr, mmax, cm-1): 3,450, 3,310 (NH2), 1,723 (C=O), 1,600
1
(C=N), 539, 558 (C–Br); H NMR (400 MHz, DMSO-d6): d (ppm) 8.01 (s, 1H),
8.08 (s, 1H), 8.15 (s, 1H), 8.42 (s, 1H), 8.75 (s, 2H); MS (ESI) m/z: 449 [M ? H]?;
Anal. calcd. for C12H6Br2N2O2Se: C, 32.10; H, 1.35; N, 6.24. Found: C, 32.32; H,
1.16; N, 6.42.
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G. Ramesh et al.
3-(2-Aminothiazol-4-yl)-6-methoxy-2H-chromen-2-one (15a)
Yellow solid; IR (KBr, mmax, cm-1): 3,463, 3,352 (NH2), 1,712 (C=O), 1,616 (C=N),
1,270 (C–O–C); 1H NMR (400 MHz, DMSO-d6): d (ppm) 3.90 (s, 3H), 7.27–7.35 (m,
5H), 7.49 (s, 1H), 8.45 (s, 1H); MS (ESI) m/z: 275 [M ? H]?; Anal. calcd. for
C13H10N2O3S: C, 56.92; H, 3.67; N, 10.21. Found: C, 57.14; H, 3.45; N, 10.39.
6-Methoxy-3-(2-(phenylamino)thiazol-4-yl)-2H-chromen-2-one (15b)
Yellow solid; IR (KBr, mmax, cm-1): 3,313 (NH), 1,708 (C=O), 1,606 (C=N), 1,276
(C–O–C); 1H NMR (400 MHz, DMSO-d6): d (ppm) 3.94 (s, 3H), 7.00 (t,
J = 7.2 Hz, 1H), 7.32–7.40 (m, 4H), 7.49–7.51 (m, 1H), 7.75 (d, J = 7.6 Hz, 2H),
7.79 (s, 1H), 8.66 (s, 1H), 10.35 (s, 1H); MS (ESI) m/z: 351 [M ? H]?; Anal. calcd.
for C19H14N2O3S: C, 65.13; H, 4.03; N, 7.99. Found: C, 65.01; H, 4.19; N, 7.83.
3-(2-Amino-1,3-selenazol-4-yl)-6-methoxy-2H-chromen-2-one (15c)
Yellow solid; IR (KBr, mmax, cm-1): 3,453, 3,344 (NH2), 1,710 (C=O), 1,617
(C=N), 1,271 (C–O–C); 1H NMR (400 MHz, DMSO-d6): d (ppm) 3.93 (s, 3H), 7.18
(d, J = 7.2 Hz, 1H), 7.70 (d, J = 7.2 Hz, 1H), 7.94 (s, 1H), 8.20 (s, 1H), 8.49 (s,
1H), 8.63 (s, 2H); MS (ESI) m/z: 321 [M]?; Anal. calcd. for C13H10N2O3Se: C,
48.61; H, 3.14; N, 8.72. Found: C, 48.38; H, 3.29; N, 8.91.
2-(2-Aminothiazol-4-yl)-3H-benzo[f]chromen-3-one (16a)
Yellow solid; IR (KBr, mmax, cm-1): 3,358, 3,292 (NH2), 1,702 (C=O), 1,632
(C=N); 1H NMR (400 MHz, DMSO-d6): d (ppm) 7.60–7.67 (m, 4H), 7.81 (t,
J = 8.4 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 8.19–8.22 (m, 2H), 8.44 (d, J = 8.4 Hz,
1H), 9.24 (s, 1H); MS (ESI) m/z: 295 [M ? H]?; Anal. calcd. for C16H10N2O2S: C,
65.29; H, 3.42; N, 9.52. Found: C, 65.42; H, 3.25; N, 9.79.
2-(2-(Phenylamino)thiazol-4-yl)-3H-benzo[f]chromen-3-one (16b)
Yellow solid; IR (KBr, mmax, cm-1): 3,303 (NH), 1,726 (C=O), 1,698 (C=N); 1H NMR
(400 MHz, DMSO-d6): d (ppm) 7.04 (t, J = 7.2 Hz, 1H), 7.44 (t, J = 8.0 Hz, 2H),
7.62–7.69 (m, 2H), 7.78–7.87 (m, 4H), 8.10 (d, J = 8.0 Hz, 1H), 8.21 (d, J = 9.2 Hz, 1H),
8.42 (d, J = 8.4 Hz, 1H), 9.35 (s, 1H), 10.43 (s, 1H); MS (ESI) m/z: 371 [M ? H]?; Anal.
calcd. for C22H14N2O2S: C, 71.33; H, 3.81; N, 7.56. Found: C, 71.50; H, 3.92; N, 7.34.
2-(2-Amino-1,3-selenazol-4-yl)-3H-benzo[f]chromen-3-one (16c)
Yellow solid; IR (KBr, mmax, cm-1): 3,230, 3,170 (NH2), 1,709 (C=O), 1,620
1
(C=N); H NMR (400 MHz, DMSO-d6): d (ppm) 7.68 (s, 1H), 7.81 (t, J = 8 Hz,
2H), 8.09 (d, J = 8.8 Hz, 2H), 8.25 (d, J = 9.2 Hz, 1H), 8.66 (d, J = 8.4 Hz, 1H),
9.08 (s, 2H), 9.28 (s, 1H); MS (ESI) m/z: 341 [M]?; Anal. calcd. for C16H10N2O2Se:
C, 56.32; H, 2.95; N, 8.21. Found: C, 56.53; H, 2.65; N, 8.36.
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Green approach
X
N
O
X
Br
)))
R'
Water,
25 oC, 10-30 sec
+
H2N R'
R
R
1a-h
2a-c
3(a-c) - 10(a-c)
R = H / F / Cl / Br / CH3 / OCH3 /NO2 / C6H5; R' = NH2 / NHPh; X = S / Se
Scheme 1 Synthesis of 2,4-disubstituted-1,3-thiazoles and selenazoles with phenacyl bromides (1a–h)
X
N
R1
R1
R3
O
O
R'
R2
R2
Br
X
)))
Water,
25 oC, 40-60 sec
+
H2N R'
O
O
O
R2
1i-n
2a-c
11(a-c) - 16(a-c)
R1 = H; R2 = H / Cl / Br / OCH3; R1 - R2 = Benzo; R3 = H / Br
R' = NH2 / NHPh; X = S / Se
Scheme 2 Synthesis of 2,4-disubstituted-1,3-thiazoles and selenazoles with 3-(2-bromoacetyl)coumarins
(1i–n)
Table 1 Optimizing the reaction conditions
Entry
Solvent
Ultrasound
frequency (kHz)
Bath
temperature (°C)
Time (s)
Yielda (%)
1
Water
30
30
30
30
30
30
30
50
50
50
50
25
25
25
25
25
40
60
25
40
60
25
10
96
93
86
88
86
95
93
98
96
93
91
2
Methanol
60
3
Acetic acid
Acetonitrile
Dimethylformamide
Water
120
120
160
10
4
5
6
7
Water
10
8
Water
10
9
Water
10
10
11
Water
10
Water:methanol (1:1 v/v)
40
Reaction conditions: Phenacyl bromide (1a, 1 mmol), thiourea (2a, 1 mmol), solvent (1 mL), ultrasonic
irradiation
a
Isolated yields
Results and discussion
The schematic representation for the formation of 2,4-disubstituted-1,3-thiazoles
and selenazoles (3–16) is shown in Schemes 1 and 2. Various phenacyl bromides
(1a–h) and 3-(2-bromoacetyl)coumarins (1i–n) on condensation with thiourea (2a),
phenylthiourea (2b) and selenourea (2c) in aqueous medium under ultrasonic
123

G. Ramesh et al.
irradiation at ambient temperature afforded the corresponding thiazoles and
selenazoles (3–16) with excellent yields (90–99 %) in short reaction times
(10–60 s). 3-(2-Bromoacetyl)coumarins (1i–n) were synthesized according to the
literature procedure [39].
In order to find the optimal conditions, a model reaction between equimolar
quantities of phenacyl bromide (1a) and thiourea (2a) was performed in different
solvents like water, methanol, acetic acid, acetonitrile and dimethylformamide at
25 °C bath temperature and 30 kHz ultrasonic frequency. We observed maximum
yield (96 %) of the product (3a) in aqueous medium within 10 s. To improve the
yield of the product in aqueous medium, the reaction was carried at 40 and 60 °C
bath temperatures, but we observed slight decreases in the yield of the product,
which may due to the formation of unidentified impurities. The same reaction was
Table 2 Synthesis of 2,4-disubstituted-1,3-thiazoles and selenazoles (3–10) with phenacyl bromides
Product
R
R’
X
Time (sec)
Yielda (%)
Melting point (°C)
Observed
Literature value [Ref]
3a
3b
3c
H
NH2
S
10
10
10
25
25
15
20
25
20
25
30
25
15
20
15
10
15
10
30
30
25
20
25
20
98
96
97
95
92
95
99
96
97
95
93
97
96
91
92
98
94
97
91
91
91
94
90
94
152–153
133–135
132–133
117–118
111–112
119–120
166–168
144–146
156–157
182–183
230–232
176
150–152 [40]
134–136 [40]
132 [31]
H
NHPh
NH2
S
H
Se
S
4a
4b
4c
F
NH2
119–120 [34]
110–111 [37]
–
F
NHPh
NH2
S
F
Se
S
5a
5b
5c
Cl
NH2
166–168 [40]
145–146 [40]
155 [31]
Cl
NHPh
NH2
S
Cl
Se
S
6a
6b
6c
Br
NH2
182–184 [40]
230–232 [40]
177–178 [40]
135–136 [40]
102–103 [40]
166 [31]
Br
NHPh
NH2
S
Br
Se
S
7a
7b
7c
CH3
CH3
CH3
OCH3
OCH3
OCH3
NO2
NO2
NO2
C6H5
C6H5
C6H5
NH2
136–137
102–104
167–168
202–204
136–138
194–196
284–285
204–206
269–270
234–236
222–224
135–136
NHPh
NH2
S
Se
S
8a
8b
8c
NH2
204–206 [40]
137–138 [40]
173 [31]
NHPh
NH2
S
Se
S
9a
9b
9c
NH2
284–286 [40]
206–207 [40]
250 [31]
NHPh
NH2
S
Se
S
10a
10b
10c
NH2
–
NHPh
NH2
S
–
Se
–
Reaction conditions: Phenacyl bromides (1a–h, 1 mmol), thiourea/phenylthiourea/selenourea (2a–c,
1 mmol), water (1 mL), ultrasonic irradiation at 50 kHz and 25 °C bath temperature
a
Isolated pure products yield
123

Green approach
Table 3 Synthesis of 2,4-disubstituted-1,3-thiazoles and selenazoles with 3-(2-bromoacetyl)coumarins
(11–16)
Product R1 R2
R3 R0
X
Time (sec) Yielda (%) Melting point (°C)
Observed Lit. [Ref.]
11a
11b
11c
12a
12b
12c
13a
13b
13c
14a
14b
14c
15a
15b
15c
16a
16b
16c
H
H
H
H
H
H
H
H
H
H
H
NH2
S
S
40
45
98
94
96
98
96
99
97
95
94
92
92
94
99
96
97
93
93
93
227–228
188–190
218–220
206–208
215–217
305–307
210–212
229–231
346–348
277–279
225–227
326–328
256–258
222–223
237–239
287–289
262–264
358–360
228–229 [40]
H
H
NHPh
NH2
188–190 [40]
H
H
Se 40
217–218 [40]
H
Cl
NH2
S
S
55
60
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
H
Cl
NHPh
NH2
H
Cl
Se 50
H
Br
NH2
S
S
55
55
H
Br
NHPh
NH2
H
Br
Se 50
H
Br
Br NH2
Br NHPh
Br NH2
S
S
60
60
H
Br
H
Br
Se 60
H
OCH3
OCH3
OCH3
H
H
H
H
H
H
NH2
S
S
45
45
H
NHPh
NH2
H
Se 40
Benzo
Benzo
Benzo
NH2
S
S
55
60
NHPh
NH2
Se 55
Reaction conditions: 3-(2-bromoacetyl)coumarin (1i–n, 1 mmol), thiourea/phenylthiourea/selenourea
(2a–c, 1 mmol), water (1 mL), ultrasonic irradiation at 50 kHz and 25 °C bath temperature
a
Isolated pure products yield
also carried out at 50 kHz ultrasonic frequency by varying the bath temperature (25,
40 and 60 °C), and observed maximum yield (98 %) of the product at 25 °C bath
temperature. We also observed the decrease in the yield of the product as the
temperature increased to 60 °C (Table 1). Recently, our group has reported the
synthesis of 1,3-thiazoles and selenazoles in a methanol–water (1:1 v/v) solvent
system [40]. Therefore, we also tested the above reaction in methanol–water (1:1
v/v) at 50 kHz ultrasonic frequency and 25 °C bath temperature, but observed only
91 % of the product yield even after 60 s. The increase in yield of the product under
ultrasonic irradiation can be explained by the cavitations effect (supporting file).
Utilizing these optimal conditions (ultrasonication at 50 kHz frequency and
25 °C bath temperature in aqueous medium), a series of 1,3-thiazoles and
selenazoles (3–16) have been synthesized by the reaction of phenacyl bromides
(1a–h) and 3-(2-bromoacetyl)coumarins (1i–n) with thiourea (2a), phenylthiourea
(2b) and selenourea (2c) in excellent yields (Tables 2 and 3). All the newly
synthesized compounds were characterized by their spectral and analytical studies,
and the known compounds were confirmed by comparing their melting points with
the reported values.
123

G. Ramesh et al.
Conclusion
In conclusion, we have efficiently synthesized a series of 2,4-disubstituted-1,3-
thiazoles and selenazoles in aqueous medium under ultrasonic irradiation at ambient
temperature. This non-conventional methodology has many advantages over
conventional reported methods that include environmentally friendly, rapid reaction
completion, easy workup procedure and analytically pure product formation in
excellent yields. This method can be effectively used for large-scale production of
thiazoles and selenazoles in shorter reaction times.
Acknowledgments We would like to thank the Director, National Institute of Technology, Warangal
for providing research facilities. One of the authors R.G. thanks the Ministry of Human Resource
Development for financial support.
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