An efficient PEG-400 mediated catalyst free green synthesis of 2-amino-thiazoles from α-diazoketones and thiourea

Article abstract of DOI:10.1007/s12039-016-1130-0

A simple and efficient method has been developed for the synthesis of 2-aminothiazoles from α-diazoketones using PEG-400 solvent system. This novel synthetic approach involves the reaction between thiourea and α-diazoketones in PEG-400 at 100 °C to yield the corresponding 2-aminothiazoles in good yields. The method is simple, rapid and generates thiazole derivatives in excellent yields without the use of any catalysts. This green protocol can be utilized for fast synthesis of various 2-aminothiazoles in good yields. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s12039-016-1130-0

J. Chem. Sci. ꢀc Indian Academy of Sciences.
DOI 10.1007/s12039-016-1130-0
An efficient PEG-400 mediated catalyst free green synthesis
of 2-amino-thiazoles from α-diazoketones and thiourea
a,∗
b
a
a
B HARI BABU
, K VIJAY , K BALA MURALI KRISHNA , N SHARMILA and
a
M BABY RAMANA
a
Department of Chemistry, Acharya Nagarjuna University, N Nagar, Andhra Pradesh, 522 510 India
College of Pharmaceutical Sciences, Acharya Nagarjuna University, N Nagar, Andhra Pradesh, 522 510 India
b
e-mail: dr.b.haribabu@gmail.com
MS received 14 September 2015; revised 13 June 2016; accepted 14 June 2016
Abstract. A simple and efficient method has been developed for the synthesis of 2-aminothiazoles from
α-diazoketones using PEG-400 solvent system. This novel synthetic approach involves the reaction between
◦
thiourea and α-diazoketones in PEG-400 at 100 C to yield the corresponding 2-aminothiazoles in good yields.
The method is simple, rapid and generates thiazole derivatives in excellent yields without the use of any
catalysts. This green protocol can be utilized for fast synthesis of various 2-aminothiazoles in good yields.
Keywords. 2-amino thiazole; α-diazoketone; PEG-400; green synthesis.
1
. Introduction
and 1100 series Agilent HPLC pump. The percentage of
C, N, S and H were calculated by elemental analysis.
Heterocyclic amines such as 2-amino thiazoles are very
interesting compounds as they are found to be useful in
1
2
3
thetreatmentofallergies, hypertension, inflammation, 2.2 General procedure
4
5
6
schizophrenia, as antibiotics and for HIV infections.
Further, their antitumor properties and in vivo
bacteriocidal activities make them more useful. There
are several methods reported in literature for the preparation
7
(i) Preparation of α-diazoketones: The starting
10
8
α-diazoketones were prepared by the condensation of
the respective acid chlorides (1 eq) with diazomethane
o
9
(4 eq) at 0 C in diethyl ether. (ii) Synthesis of thia-
of 2-aminothiazoles involving the use of Lewis acids,
zoles: A mixture of α-diazoketone (1 mmol), thiourea
Bronsted acids or inorganic salts as the catalysts in
organic solvent medium. However, many of these
methods suffer from lower yields, long reaction times,
usage of organic solvents and harsh reaction conditions.
(
1 mmol) in 10 mL of polyethylene glycol was heated
◦
at 100 C for the appropriate time (Table 1). After the
completion of the reaction as indicated by TLC,
the reaction mixture was quenched with water and
extracted with ethyl acetate (2x15 mL). The combined
2. Experimental
organic layers were dried over anhydrous Na SO and
2 4
the solvent was evaporated. The crude residue was
purified on silica gel chromatoghraphy (Merck, 100–200
mesh, ethyl acetate–hexane, 3:7) to afford the pure
2
.1 Materials and Methods
All the chemicals used were of AR grade of Merck
manufactures. Reagent grade solvents (E. Merck) were
used as such. All the melting points were obtained from
2-aminothiazole.
Remi melting point apparatus. All reactions were monitored 2.3 Spectral data for selected products
by TLC and all yields refer to isolated products after
column chromatography. Proton NMR spectra were 2.3a 4-Phenylthiazol-2-amine (entry 1): Pink colored
◦
recorded in CDCl or DMSO-d on Bruker 400 MHz solid. M.p. 149–150 C; IR (KBr): 3434, 3254, 3154,
3
6
13
and C NMR spectra was on Bruker 100 MHz, Mass 3113, 2924, 2368, 1598, 1517, 1480, 1439, 1332,
−1
1
spectral studies were carried out on LC-MS system 1196, 1070, 1023, 909, 843, 770, 713 cm ; H NMR
equipped with Agilent 1100 series, LC/MSD detector (300 MHz, CDCl
+ DMSO): δ 7.73 (d, J = 7.8 Hz,
H), 7.36–7.17 (m, 3H), 6.63 (s, 1H) 6.21 (br s, 2H);
3
2
∗
13
For correspondence
C NMR (75 MHz, CDCl + DMSO): d 167.3,
3

B Hari Babu et al.
Table 1. Synthesis of 2-aminothiazoles using polyethylene glycol (PEG-400) medium.
Entry
α-diazoketone
2-aminothiazole
Time (h)
2
Yield (%)
96
1
2
3
4
5
2
91
87
90
93
3.5
3.5
2.5
6
7
8
9
2.5
3.0
3.0
95
92
90
3.0
4.0
94
91
10
a
1
All products were characterized by H NMR, Mass spectroscopy.
Yield after silica gel column chromatography.
b

Green synthesis of 2-aminothiazoles
1
49.1, 133.7, 127.2, 126.0, 124.5, 100.1; ESI-MS (m/z):
NH
2
N
(
M+H) 177; HRMS found for C H N S: 177.0488.
O
9
8
2
S
N2
S
PEG 400
o
+
H
2
N
NH
2
1
00 C
Me
Me
2.3b 4-(4-flouro phenyl)-1, 3-thiazol-2-amine (4):
3b
1
2
◦
White Solid, M.p. 178–180 C; IR (KBr): 3425, 2923,
1
−
1 1
598, 1505, 744 cm ; H NMR (CDCl , 300 MHz): δ
3
Scheme 1. PEG-400 mediated synthesis of 2-amino-4-
5
.51 (brs, 2H), 6.55 (s, 1H), 7.03(t, 2H), 7.68 (m, 2H); tolylthiazole 3b.
+
Mass (ESI): 217 [M+Na] ; Anal. found for C H FNS:
10
8
C, 54.53; H, 4.42; N, 14.13; S, 16.38.
Various substituents on α-diazoketones, such as
electron donating and electron withdrawing groups did
not affect the efficiency of the reaction and the reactions
proceeded smoothly to afford the corresponding
aminothiazoles in excellent yield. The reaction yields
were not affected even when halogen substituents were
present on diazoketone. All resulting compounds were
2
.3c 4-Pentadecylthiazol-2-amine(entry9): Colorless
◦
solid. M.p. 65–66 C; IR (KBr): 3430, 3233, 3065, 2920,
2850, 1607, 1541, 1511, 1467, 1377, 1317, 1112, 1021,
−1
1
967, 847, 720, 698, 632 cm ; H NMR (300 MHz,
DMSO): δ 0.91 (t, J = 7.0 Hz, 3H), 1.29 (br s, 24H),
1
confirmed by their H NMR and mass spectroscopic
data.
1
6
.55–1.65 (m, 2H), 2.43 (t, 2H, J = 7.0 Hz), 5.90 (s, 1H),
13
.31 (br s, 2H); C NMR (75 MHz, CDCl + DMSO):
3
d 167.1, 151.5, 99.0, 33.2, 30.5, 30.3, 28.3, 27.4, 23.7,
2
1.3, 12.9; EIMS (m/z): (M+H): 311.40.
4
. Conclusions
In conclusion, we report an inexpensive, fast and
efficient synthesis of 2-aminothiazoles from α-
diazoketones using polyethylene glycol (PEG-400)as
an efficient solvent medium. This procedure is a very
attractive and useful alternative method to the other
existing methods for the synthesis of 2-aminothiazoles.
2
.3d 4-tert-butylthiazol-2-amine (10): Viscous Liquid,
−1 1
IR (KBr) 3438, 3279, 3163, 2961, 1524 cm ; H NMR
(CDCl , 200 MHz): δ 1.24 (s, 9H), 5.09 (brs, 2H),
3
+
6
.02 (s, 1H); EIMS(m/z):156 [M ]; Anal. found for
C H N S: C, 53.62; H, 7.63; N, 17.99; S, 20.61.
7
12
2
3
. Results and discussion
Supplementary Information (SI)
The synthesis of 2-aminothiazoles still has great
importance. The usage of green reagents and solvents
or solvent free conditions has attracted more attention
in recent literature due to environmental concerns. The
PEG was utilized as a mild, and highly efficient solvent
system for the synthesis of benzimidazoles in excellent
yields from o-phenyldiamine and a wide variety of aryl
aldehydes using CAN as catalyst.1
Figures S1–S11 are provided in the supporting informa-
tion available at www.ias.ac.in/chemsci.
Acknowledgements
Authors are thankful to Acharya Nagarjuna University,
Guntur for constant encouragement and CSIR, New
Delhi (EMR-II, 02/198) for financial assistance.
1
In the present investigation, we report a versatile,
environmentally friendly green synthesis of 2-amino-
thiazoles in polyethylene glycol medium. PEG-400 is References
a more effective and useful medium due to its environ-
mental benign nature, ease of handling and lower cost.
The reaction was carried out by heating α-diazoketone
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◦
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ponding 2-aminothiazoles. In all these cases, reactants
were completely converted into the corresponding
2-aminothiazoles with excellent yields (Table 1).

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