One-pot three-component reaction of arylglyoxals with acetylthiourea and Meldrum’s acid or barbituric acid for synthesis of new 2-acetamido-4-arylthiazol-5-yl derivatives

Article abstract of DOI:10.1080/17415993.2019.1602127

An efficient method for the synthesis of 2-acetamido-4-arylthiazol-5-yl derivatives via a novel one-pot three-component reaction of arylglyoxals, 1,3-dicarbonyl compounds such as Meldrum’s acid or barbituric acid, and acetylthiourea in ethanol is reported

Full text of DOI:10.1080/17415993.2019.1602127

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: https://www.tandfonline.com/loi/gsrp20
One-pot three-component reaction of arylglyoxals
with acetylthiourea and Meldrum’s acid or
barbituric acid for synthesis of new 2-acetamido-4-
arylthiazol-5-yl derivatives
Farzaneh Alizadeh-Bami, Hossein Mehrabi & Reza Ranjbar-Karimi
To cite this article: Farzaneh Alizadeh-Bami, Hossein Mehrabi & Reza Ranjbar-Karimi (2019):
One-pot three-component reaction of arylglyoxals with acetylthiourea and Meldrum’s acid or
barbituric acid for synthesis of new 2-acetamido-4-arylthiazol-5-yl derivatives, Journal of Sulfur
Chemistry, DOI: 10.1080/17415993.2019.1602127
To link to this article: https://doi.org/10.1080/17415993.2019.1602127
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2019.1602127
One-pot three-component reaction of arylglyoxals with
acetylthiourea and Meldrum’s acid or barbituric acid for
synthesis of new 2-acetamido-4-arylthiazol-5-yl derivatives
Farzaneh Alizadeh-Bami , Hossein Mehrabi and Reza Ranjbar-Karimi
Department of Chemistry, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran
ABSTRACT
ARTICLE HISTORY
Received 6 January 2019
Accepted 19 March 2019
An efficient method for the synthesis of 2-acetamido-4-arylthiazol-
5-yl derivatives via a novel one-pot three-component reaction of
arylglyoxals, 1,3-dicarbonyl compounds such as Meldrum’s acid or
barbituric acid, and acetylthiourea in ethanol is reported.
KEYWORDS
Meldrum’s acid; barbituric
acid; acetylthiourea;
arylglyoxal; 2-acetamido-4-
arylthiazol-5-yl; one-pot
three-component reaction
1. Introduction
Thiazoles are one of the most important five membered heterocyclic compounds con-
taining sulfur that show a broad range of pharmaceutical and biological applications [1].
Thiazole derivatives exhibit antifungal [2,3], antitumor [4,5], antibacterial [6], antioxidant
[7,8], anthelmintic [9], and anti-obesity [10], biological activities which have identified
them as new candidates in cancer treatment [11]. Moreover, thiazole cores can be identi-
fied in the structure of different drugs, for example ritonavir is a potent inhibitor of HIV
protease [12], thiamine is vitamin B1 [13], bleomycin is an antibiotic [14], tiazofurin is an
antineoplastic [15], and febuxostat is used for treatment of chronic gout [16]. Therefore,
these compounds could find applications in dermatology, especially in cosmetic and sun-
screens [17]. Also some of these thiazoles are used as LbSOD inhibitors [18], liquid crystals
[19], and fluorescent dyes [20,21]. As a result, studies on preparation of thiazole derivatives
have received high importance in organic synthesis.
CONTACT Hossein Mehrabi
mehraby_h@yahoo.com
Department of Chemistry, Vali-e-Asr University of
Rafsanjan, Rafsanjan 77176, Iran
This article makes reference to supplementary material available on the publisher’s website at
http://doi.org/10.1080/17415993.2019.1602127
© 2019 Informa UK Limited, trading as Taylor & Francis Group

2
F. ALIZADEH-BAMI ET AL.
The classical methods for synthesize of thiazole derivatives included Hantzsch synthe-
sis [22], and the Gabriel synthesis [23]. Recently, various synthetic methods have been
reported for the construction of thiazoles; these synthetic strategies include: multi-step
[24–26], multicomponent reaction [27,28], cyclocondensation [29], microwave heating
[30], and tandem processes from various starting materials [31,32]. Also for some of these
synthesis catalysis [33–37], and oxidants [38] are used.
A few reports have appeared on the synthesis of thiazoles, which include solid phase
synthesis [39–43], and various other methods [44–47]. Although these methods are effec-
tive for certain substrates, the development of general procedures for the synthesis of highly
functionalized thiazole derivatives from readily available starting materials still remains an
important task in organic chemistry. With this background in mind and in continuation
of our previous work on the development of multicomponent approaches for the synthesis
of organic sulfur compounds [48,49], we herein report an efficient and simple method for
synthesis of new thiazole derivatives (Table 2) from a one-pot three-component reaction
of arylglyoxals with acetylthiourea and Meldrum’s acid or barbituric acid in presence of
triethylamine in ethanol under reflux conditions.
2. Results and discussion
To find the optimal conditions, we studied the synthesis of ethyl 2-(2-acetamido-4-(4-
chlorophenyl)thiazol-5-yl)acetate 4a from the condensation of 4-chlorophenylglyoxal 1a,
Meldrum’s acid 2, and acetylthiourea 3 with two drops of Et3N, under various reaction
conditions (Table 1).
The optimization of the reaction conditions, including the reaction solvent, the reaction
temperature, and the equivalents of starting materials were investigated. First, various sol-
vents were examined (Table 1, entries 1–4), and ethanol was shown to be the preeminent
Table 1. Optimization of the reaction conditions.
Entry
Solvent
Temp.a
mmol of 1a:2:3
Yield (%)b
1
2
3
4
5
6
7
8
DMF
MeCN
H2O
EtOH
DMF
MeCN
H2O
EtOH
EtOH
EtOH
EtOH
EtOH
r.t.
r.t.
r.t.
1:1:1
1:1:1
1:1:1
1:1:1
1:1:1
1:1:1
1:1:1
1:1:1
1:1.2:1.2
1.2:1:1.2
1.2:1.2:1
1.2:1.2:1
N.R.
N.R.
N.R.
22
Trace
Trace
Trace
62
46
50
80
80
r.t.
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Refluxc
9
10
11
12
aReaction conditions: solvent was 15 ml, reaction time was 3 h, with two drops of Et3N.
bIsolated yields.
cReaction time was 12 h.

JOURNAL OF SULFUR CHEMISTRY
3
Table 2. Synthesis of 2-acetamido-4-arylthiazol-5-yl derivatives.
Product
4a
Ar
2 or 5
Time (min)
125
Yield (%)a
80
4-ClC6H4
4b
4c
4d
4e
4f
4-BrC6H4
4-CH3OC6H4
4-CH3C6H4
C6H5
136
180
150
145
120
76
58
62
70
82
4-FC6H4
6a
6b
6c
6d
4-ClC6H4
4-CH3C6H4
4-BrC6H4
15
22
18
26
15
90
85
87
85
92
4-CH3OC6H4
6e
4-FC6H4
aIsolated yields.

4
F. ALIZADEH-BAMI ET AL.
solvent for this reaction. Then, we examined the influence of different temperatures on this
reaction. To our satisfaction, when the reaction was carried out for 3 h at room tempera-
ture, the product formed in 22% yield, but under reflux conditions in the same time, the
product was formed in 62% yield (Table 1, entries 4 and 8). Finally, we observed that the
amount of starting materials also have important influence on the reaction (Table 1, entries
8–11). A larger amount of 4-chlorophenylglyoxal 1a, and Meldrum’s acid 2 (for example,
1.2 mmol) in ethanol at reflux temperature resulted in a higher yield, 80% (Table 1, entry
11). On the other hand, increasing the reaction time in ethanol under reflux condition
did not improve the yield (Table 1, entry 12). This series of experiments reveal that the
optimal results were obtained when the reaction of 4-chlorophenylglyoxal 1a (1.2 mmol)
was conducted with Meldrum’s acid 2 (1.2 mmol), acetylthiourea 3 (1.0 mmol), and two
drops of triethylamine in ethanol under reflux conditions. Under these optimized condi-
tions, the yield of 4a reached 80%. These optimized reaction conditions (Table 1, entry
11), were then used to synthesize and explore the scope of this novel transformation with
various 1,3-dicarbonyl compounds such as Meldrum’s acid or barbituric acid, arylglyox-
als, and acetylthiourea to give two series of 2-acetamido-4-arylthiazol-5-yl derivatives 4a-f
and 6a-e (Table 2) in good yields.
Under the optimized reaction conditions, two series of 2-acetamido-4-arylthiazol-5-yl
derivatives 4a–f and 6a–e were synthesized by the reaction of 1,3-dicarbonyl compounds
such as Meldrum’s acid 2 or barbituric acid 5 with arylglyoxals 1 and acetylthiourea 3
to give the corresponding products. As can be seen from Table 2, the structural type
of 2-acetamido-4-arylthiazol-5-yl derivative, 4 or 6, are dependent on the nature of the
1,3-dicarbonyl compounds. When the arylglyoxal especially with electron-withdrawing
groups and the 1,3-dicarbonyl compounds such as barbituric acid were employed, a lower
reaction time was required.
To the best of our knowledge, all the synthesized compounds are novel and were char-
1
acterized by H and 13C NMR, IR, CHN analysis and melting points. For instance, the
1H NMR spectrum of the compound 4a consisted of a triplet at δ = 1.30 ppm with a cou-
pling constant of 7.0 Hz for the methyl protons and a singlet at δ = 1.68 ppm for another
methyl group was observed. A singlet that integrated for two protons was observed at
δ = 3.81 ppm for the methylene protons. In addition, a quartet at δ = 4.24 ppm with cou-
pling constant of 7.0 Hz for two protons was observed. Also, two doublet signals at δ = 7.42
and 7.53 ppm with coupling constant of 8.5 Hz for the aromatic protons of the phenyl ring
and a broad singlet signal at δ = 11.19 ppm for the proton of the nitrogen group were also
observed. The 1H decoupled 13C NMR spectrum of compound 4a showed 13 distinct sig-
nals in agreement with the proposed structure. Partial assignment of these resonances for
the other products is given in the experimental section.
A proposed mechanism for the formation of 2-acetamido-4-arylthiazol-5-yl deriva-
tives 4 and 6 is described in Scheme 1. The reaction of 1,3-dicarbonyl compounds such
as Meldrum’s acid 2 or barbituric acid 5 with arylglyoxal 1 in the presence of triethy-
lamine gave the intermediate A. After the addition of acetylthiourea 3, the formation
of intermediate B occurred via a Michael addition reaction of the sulfur anion at the
sp2 carbon atom of A. Also, intermediate B undergoes nucleophilic addition of the
nitrogen anion to the carbonyl group then elimination of H2O affording the intermedi-
ates C or its tautomer D. In the last step, the nature of the 1,3-dicarbonyl compounds
were different, so that; ethyl 2-(2-acetamido-4-arylthiazol-5-yl)acetate 4 is formed by

JOURNAL OF SULFUR CHEMISTRY
5
Scheme 1. The proposed mechanism for the synthesis of 2-acetamido-4-arylthiazol-5-yl derivatives.
ethanolysis of Meldrum’s acid by elimination of acetone and CO2 in ethanol at reflux
conditions and N-(5-(2,2-diethoxy-6-hydroxy-4-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-
4-arylthiazol-2-yl)acetamide 6 is formed by formation of a ketal from the carbonyl group
of barbituric acid with ethanol and elimination of H2O in ethanol under reflux conditions.
3. Conclusions
We have successfully developed an efficient one pot, three-component reaction of 1,3-
dicarbonyl compounds such as Meldrum’s acid or barbituric acid with arylglyoxals and
acetylthiourea for the synthesis two series of 2-acetamido-4-arylthiazol-5-yl derivatives.
Moreover, the method has advantages in terms of mild reaction conditions, low cost
of the starting materials, short reaction time, operational simplicity, good yields, and
environmental friendliness.
4. Experimental
4.1. General
All chemicals were purchased from Aldrich and Merck with high-grade quality, and used
without any purification. All melting points were obtained by Barnstead Electrothermal
9200 apparatus and are uncorrected. The reactions were monitored by TLC and all yields
refer to isolated products. NMR spectra were obtained on a Varian 500 MHz spectrometer
(1H NMR at 500 MHz, 13C NMR at 125 MHz) in CDCl3 using TMS as an internal standard.
Infrared spectra were recorded on a Bruker FT-IR Equinax-55 spectrophotometer in KBr
with absorption in cm−1. Elemental analyses were performed using a Carlo Erba EA 1108
instrument. All products were characterized by their spectral and physical data.

6
F. ALIZADEH-BAMI ET AL.
4.2. General procedure for the preparation of compounds 4a-f
A mixture of arylglyoxal 1 (1.2 mmol), Meldrum’s acid 2 (1.2 mmol), and acetylthiourea 3
(1.0 mmol) was stirred in 15.0 mL of ethanol, in the presence of two drops of Et3N under
reflux conditions for 120–180 min. After completion of the reaction, determined by TLC,
the solvent was removed under reduced pressure and the resulting crude product was
recrystallised from ethanol to give the pure compounds 4a–f (58–82%).
4.3. General procedure for the preparation of compounds 6a-e
A mixture of arylglyoxal 1 (1.2 mmol), barbituric acid 5 (1.2 mmol), and acetylthiourea 3
(1.0 mmol) was stirred in 15.0 mL of ethanol, in the presence of two drops of Et3N under
reflux conditions for 15–26 min. After completion of the reaction, determined by TLC,
the solvent was removed under reduced pressure and the viscous residue was purified by
plate chromatography (20 × 20 cm) using n-hexane–EtOAc (2:1) as eluent to give the pure
compounds 6a–e (85–92%).
4.3.1. Ethyl 2-(2-acetamido-4-(4-chlorophenyl)thiazol-5-yl)acetate (4a)
1
Yellow oil; IR υ/cm−1 (KBr): 3447, 2918, 1733, 1548. H NMR (500 MHz, CDCl3):
δ = 1.30 (t, J = 7.0 Hz, 3H, CH3), 1.68 (s, 3H, CH3), 3.81 (s, 2H, CH2), 4.24 (q, J = 7.0 Hz,
2H, CH2), 7.42 (d, J = 8.5 Hz, 2H, Ar), 7.53 (d, J = 8.5 Hz, 2H, Ar), 11.19 (bs, 1H, NH)
ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2, 22.3, 32.5, 61.6, 118.9, 129.0, 130.0, 132.7,
134.4, 145.7, 157.9, 168.2, 170.1 ppm. Anal. Calcd for C15H15ClN2O3S (338.81): C, 53.18;
H, 4.46; N, 8.27. Found: C, 53.31; H, 4.49; N, 8.25.
4.3.2. Ethyl 2-(2-acetamido-4-(4-bromophenyl)thiazol-5-yl)acetate (4b)
1
Yellow oil; IR υ/cm−1 (KBr): 3315, 2979, 1734, 1545. H NMR (500 MHz, CDCl3):
δ = 1.28 (t, J = 7.0 Hz, 3H, CH3), 1.60 (s, 3H, CH3), 3.81 (s, 2H, CH2), 4.22 (q, J = 7.0 Hz,
2H, CH2), 7.47 (d, J = 8.5 Hz, 2H, Ar), 7.58 (d, J = 8.5 Hz, 2H, Ar), 11.52 (bs, 1H, NH)
ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2, 22.2, 32.5, 61.7, 118.9, 122.6, 130.3, 132.0,
133.1, 145.7, 158.2, 168.3, 170.1 ppm. Anal. Calcd for C15H15BrN2O3S (383.26): C, 47.01;
H, 3.95; N, 7.31. Found: C, 47.06; H, 3.97; N, 7.26.
4.3.3. Ethyl 2-(2-acetamido-4-(4-methoxyphenyl)thiazol-5-yl)acetate (4c)
1
Yellow oil; IR υ/cm−1 (KBr): 3255, 2954, 1734, 1511. H NMR (500 MHz, CDCl3):
δ = 1.29 (t, J = 7.0 Hz, 3H, CH3), 1.67 (s, 3H, CH3), 3.81 (s, 2H, CH2), 3.85 (s, 3H, OCH3),
4.22 (q, J = 7.0 Hz, 2H, CH2), 6.96 (d, J = 8.5 Hz, 2H, Ar), 7.51 (d, J = 8.5 Hz, 2H, Ar),
11.49 (bs, 1H, NH) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2, 22.2, 32.6, 55.3, 61.5,
114.1, 117.3, 130.0, 130.7, 138.5, 146.6, 159.6, 168.4, 170.4 ppm. C16H18N2O4S (334.39):
C, 57.47; H, 5.43; N, 8.38. Found: C, 57.36; H, 5.42; N, 8.35.
4.3.4. Ethyl 2-(2-acetamido-4-(p-tolyl)thiazol-5-yl)acetate (4d)
1
Yellow oil; IR υ/cm−1 (KBr): 3266, 2921, 1736, 1546. H NMR (500 MHz, CDCl3):
δ = 1.29 (t, J = 7.0 Hz, 3H, CH3), 1.58 (s, 3H, CH3), 2.40 (s, 3H, CH3), 3.83 (s, 2H, CH2),
4.22 (q, J = 7.0 Hz, 2H, CH2), 7.24 (d, J = 8.0 Hz, 2H, Ar), 7.46 (d, J = 8.0 Hz, 2H, Ar),
11.49 (bs, 1H, NH) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2, 21.2, 22.1, 32.6, 61.5,

JOURNAL OF SULFUR CHEMISTRY
7
117.8, 128.7, 129.4, 131.4, 138.2, 146.9, 157.9, 168.4, 170.4 ppm. C16H18N2O3S (318.39):
C, 60.36; H, 5.70; N, 8.80. Found: C, 60.44; H, 5.73; N, 8.78.
4.3.5. Ethyl 2-(2-acetamido-4-phenylthiazol-5-yl)acetate (4e)
1
Yellow oil; IR υ/cm−1 (KBr): 3162, 2973, 1735, 1546. H NMR (500 MHz, CDCl3):
δ = 1.29 (t, J = 7.0 Hz, 3H, CH3), 1.52 (s, 3H, CH3), 3.84 (s, 2H, CH2), 4.22 (q, J = 7.0 Hz,
2H, CH2), 7.39 (t, J = 7.0 Hz, 1H, Ar), 7.44 (d, J = 7.0 Hz, 2H, Ar), 7.58 (d, J = 7.0 Hz,
2H, Ar), 11.68 (bs, 1H, NH) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.2, 21.9, 32.5, 61.5,
118.3, 128.4, 128.8, 129.5, 134.2, 146.8, 158.3, 168.5, 170.3 ppm. C15H16N2O3S (304.36):
C, 59.19; H, 5.30; N, 9.20. Found: C, 59.14; H, 5.29; N, 9.17.
4.3.6. Ethyl 2-(2-acetamido-4-(4-fluorophenyl)thiazol-5-yl)acetate (4f)
1
Yellow oil; IR υ/cm−1 (KBr): 3263, 2919, 1734, 1546. H NMR (500 MHz, CDCl3):
δ = 1.29 (t, J = 7.0 Hz, 3H, CH3), 1.93 (s, 3H, CH3), 3.79 (s, 2H, CH2), 4.22 (q, J = 7.0 Hz,
2H, CH2), 7.13 (d, J = 8.5 Hz, 2H, Ar), 7.55 (d, J = 8.5 Hz, 2H, Ar), 10.32 (bs, 1H, NH)
ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1, 22.6, 39.4, 61.6, 115.6, 122.7, 127.2, 130.5,
142.7, 145.6, 150.7, 167.8, 176.5 ppm. C15H15FN2O3S (322.35): C, 55.89; H, 4.69; N, 8.69.
Found: C, 55.97; H, 4.70; N, 8.65.
4.3.7. N-(4-(4-chlorophenyl)-5-(2,2-diethoxy-6-hydroxy-4-oxo-1,2,3,
4-tetrahydropyrimidin-5-yl)thiazol-2-yl)acetamide (6a)
White solid; Mp: >320°C. IR υ/cm−1 (KBr): 3411, 3151, 2979, 1687, 1578. 1H
NMR (500 MHz, CDCl3): δ = 1.13 (t, J = 7.5 Hz,6H, CH3), 2.12 (s, 3H, CH3), 3.04
(q, J = 7.5 Hz, 2H, CH2), 3.06 (q, J = 7.5 Hz, 2H, CH2), 7.35 (d, J = 8.5 Hz, 2H, Ar-),
7.67 (d, J = 8.5 Hz, 2H, Ar), 8.90 (bs, 1H, OH), 10.01 (bs, 2H, NH), 11.96 (bs, 1H, NH)
ppm. 13C NMR (125 MHz, CDCl3): δ = 9.1, 22.9, 46.2, 80.3, 128.3, 129.2, 131.4, 135.7,
143.9, 151.4, 156.2, 161.3, 163.2, 168.5, 168.6 ppm. C19H21ClN4O5S (452.91): C, 50.39; H,
4.67; N, 12.37. Found: C, 50.48; H, 4.70; N, 12.35.
4.3.8. N-(5-(2,2-diethoxy-6-hydroxy-4-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-
4-(p-tolyl)thiazol-2-yl)acetamide (6b)
1
White solid; Mp: >320°C. IR υ/cm−1 (KBr): 3396, 3167, 2979, 1673, 1571. H NMR
(500 MHz, CDCl3): δ = 1.12 (t, J = 6.5 Hz, 6H, CH3), 2.09 (s, 3H, CH3), 2.24 (s, 3H,
CH3), 3.03 (q, J = 6.5 Hz, 4H, CH2), 7.04 (d, J = 7.5 Hz, 2H, Ar), 7.62 (d, J = 7.5 Hz, 2H,
Ar), 8.92 (bs, 1H, OH), 9.14 (bs, 2H, NH), 11.75 (bs, 1H, NH) ppm. 13C NMR (125 MHz,
CDCl3): δ = 9.1, 21.2, 22.9, 46.2, 78.3, 116.6, 124.0, 127.6, 128.5, 134.7, 135.3, 152.4, 154.9,
164.0, 168.0, 168.1 ppm. C20H24N4O5S (432.50): C, 55.54; H, 5.59; N, 12.95. Found: C,
55.48; H, 5.62; N, 12.89.
4.3.9. N-(4-(4-bromophenyl)-5-(2,2-diethoxy-6-hydroxy-4-oxo-1,2,3,
4-tetrahydropyrimidin-5-yl)thiazol-2-yl)acetamide (6c)
1
White solid; Mp: >320°C. IR υ/cm−1 (KBr): 3384, 3149, 2980, 1680, 1578. H NMR
(500 MHz, CDCl3): δ = 1.11 (t, J = 7.0 Hz, 6H, CH3), 2.09 (s, 3H, CH3), 3.03 (q,
J = 7.0 Hz, 4H, CH2), 7.43 (d, J = 8.5 Hz, 2H, Ar), 7.66 (d, J = 8.5 Hz, 2H, Ar), 8.92
(bs, 1H, OH), 9.33 (bs, 2H, NH), 11.82 (bs, 1H, NH) ppm. 13C NMR (125 MHz, CDCl3):
δ = 9.0, 22.9, 46.1, 78.7, 119.3, 125.4, 129.5, 130.8, 136.8, 137.4, 142.2, 152.3, 155.1, 163.8,

8
F. ALIZADEH-BAMI ET AL.
168.2 ppm. C19H21BrN4O5S (497.36): C, 45.88; H, 4.26; N, 11.26. Found: C, 45.97; H, 4.29;
N, 11.18.
4.3.10. N-(5-(2,2-diethoxy-6-hydroxy-4-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-
4-(4-methoxyphenyl)thiazol-2-yl)acetamide (6d)
White solid; Mp: >320°C. IR υ/cm−1 (KBr): 3381, 3154, 3978, 1685, 1576. 1H
NMR (500 MHz, CDCl3): δ = 1.11 (t, J = 10.0 Hz, 6H, CH3), 2.10 (s, 3H, CH3),
3.01 (q, J = 7.0 Hz, 4H, CH2), 3.72 (s, 3H, OCH3), 6.83 (d, J = 8.5 Hz, 2H, Ar), 7.69 (d,
J = 8.5 Hz, 2H, Ar), 8.95 (bs, 1H, OH), 9.24 (bs, 2H, NH), 11.75 (bs, 1H, NH) ppm. 13
C
NMR (125 MHz, CDCl3): δ = 9.1, 22.9, 46.2, 55.4, 78.4, 113.4, 122.9, 128.8, 130.1, 143.7,
152.4, 154.9, 157.3, 158.1, 164.2, 168.1 ppm. C20H24N4O6S (448.49): C, 53.56; H, 5.39; N,
12.49. Found: C, 53.55; H, 5.41; N, 12.45.
4.3.11. N-(5-(2,2-diethoxy-6-hydroxy-4-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-
4-(4-fluorophenyl)thiazol-2-yl)acetamide (6e)
1
White solid; Mp: >320°C. IR υ/cm−1 (KBr): 3409, 3129, 2981, 1686, 1576. H NMR
(500 MHz, CDCl3): δ = 1.12 (t, J = 7.5 Hz, 6H, CH3), 2.10 (s, 3H, CH3), 3.02 (q,
J = 7.5 Hz, 4H, CH2), 7.08 (d, J = 9.0 Hz, 2H, Ar), 7.76 (d, J = 9.0 Hz, 2H, Ar), 8.92
(bs, 1H, OH), 9.26 (bs, 2H, NH), 11.78 (bs, 1H, NH) ppm. 13C NMR (125 MHz, CDCl3):
δ = 9.1, 22.9, 46.2, 78.3, 110.0, 114.7, 124.4, 129.4, 129.4, 134.0, 142.6, 152.4, 155.0, 164.0,
168.2 ppm. C19H21FN4O5S (436.46): C, 52.29; H, 4.85; N, 12.84. Found: C, 52.33; H, 4.87;
N, 12.80.
Acknowledgement
We are thankful to the Office of Graduate Studies of Vali-e-Asr University of Rafsanjan for partial
support of this work.
Disclosure statement
No potential conflict of interest was reported by the authors.
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