Green synthesis of 6-[2-aminothiazol-4-yl]-2-furylchromone

Article abstract of DOI:10.14233/ajchem.2014.16376

Synthesis of 2-aminothiazoles through Hantzsch method involves the use of bromine. An 2-aminothiazole system 6-[2-aminothiazol-4- yl]-2-furylchromone has been synthesized green chemically from 6-chloroacetyl-2-furylchromone and 6-acetyl-2-furylchromone during present study. The structures of new compounds were elucidated on the basis of IR and PMR-spectra.

Full text of DOI:10.14233/ajchem.2014.16376

Asian Journal of Chemistry; Vol. 26, No. 13 (2014), 3989-3991
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.16376
Green Synthesis of 6-[2-Aminothiazol-4-yl]-2-furylchromone
1
,*
2
VINAY PRABHA SHARMA and RAKESH KUMAR
1
2
Department of Chemistry, Meerut College, Meerut-250 001, India
Department of Chemistry, M.M.M. (P.G.) College, Bhatpar Rani, (Deoria), India
*
Corresponding author: E-mail: shambhavisharma98@hotmail.com
Received: 16 September 2013; Accepted: 16 January 2014;
Published online: 23 June 2014;
AJC-15389
Synthesis of 2-aminothiazoles through Hantzsch method involves the use of bromine. An 2-aminothiazole system 6-[2-aminothiazol-4-
yl]-2-furylchromone has been synthesized green chemically from 6-chloroacetyl-2-furylchromone and 6-acetyl-2-furylchromone during
present study. The structures of new compounds were elucidated on the basis of IR and PMR-spectra.
Keywords: 6-[2-Aminothiazol-4-yl]-2-furylchromone, 6-Chloroacetyl-2-furylchromone, 6-Acetyl-2-furylchromone.
O
INTRODUCTION
2
-Aminothiazoles are key compounds in the synthesis of
CH COCl
ClCH COCl,
medicinally active compounds. Thiazoles are associated with
curative effects under bad health conditions. For instance, they
3
2
(
II)
and AlCl3
AlCl3
1
-3
4-6
7-8
are anticancerous , antimicrobial , antiinflammatory ,
9-10
11
antitubercular and antifungal . Chromones are widely studied
CH CO
ClCH CO
2
3
1
2-18
compounds with broad spectrum of medicinal activities
.
Therefore, it was thought to develop 2-aminothiazole system
at 6-position of chromone. Their synthesis by Hantzsch thiazole
method involves use of the dangerous bromine. To eliminate
the use of bromine environment friendly green chemical
methods were developed according to the (Scheme-I).
First method involved synthesis of title compound 4 through
O
O
(III)
(v)
Thiourea/I2
Thiourea/ethanol
Hantzsch method)
(
(
King's procedure)
N
6
-chloroacetyl-2-furylchromone (3) which was obtained from
-furylchromone (2) by Friedel Craft reaction with chloro-
H N
2
(
IV)
2
Scheme-I
acetyl chloride in presence of anhydrous aluminium chloride
in carbon disulphide (CS ) solvent. Compound 3 upon conden-
2
-1
Absorption frequency is recorded in cm . The PMR-spectra
were recorded in CDCl and/or DMSO-d on BRUKER
sation with thiourea in ethanol yielded compound 4.
In second method, compound 4 was obtained from 6-acetyl-
3
6
AVANCE II 400 NMR spectrometer. The chemical shifts are
expressed in ppm units (d) downfield from internal tetramethyl
silane (TMS) standard. Solvents and starting materials were
purified using standard procedures. The purity of compounds
was checked on TLC-plates coated with silica gel.
2
-furylchromone (5) by King's procedure. Here, compound 5
was condensed with thiourea under solvent free condition on
water-bath by heating of 24 h. Compound 5 was prepared from
compound 2 by Friedel-Craft reaction using acetyl chloride
as acylating agent.
Synthesis of chalcone (1): Chalcone was synthesised
from o-hydroxyacetophenone and furfural according to proce-
19
dure described in literature .
Structures of compounds 3, 4 and 5 were elucidated by
elemental analysis, IR and PMR-spectral data.
Synthesis of 2-furylchromone (2): This compound was
synthesised by refluxing 2g of 1 in DMSO in presence of 2-3
crystals of iodine for 10 min according to the procedure
EXPERIMENTAL
All the melting and boiling points are uncorrected. Infrared
spectra were recorded on SPECTRUM BX SERIES in KBr.
20
described in literature .

3
990 Sharma et al.
Asian J. Chem.
Synthesis of chloroacetyl chloride: In a 250 mL round
remove unreacted acetyl compound. Now reaction mixture
was treated with hot water accompanied by agitation with glass
rod and was filtered. This process was repeated 5 times. Now
hot filtrate was treated with liquor ammonia to precipitate the
compound. Solid thus obtained was filtered, washed with water
and recrystallized from ethanol. m.p. = 318-319 ºC; yield =
2
bottom flask equipped with a reflux condenser and CaCl guard
tube was placed 0.1 mol (9.45 g) of chloroacetic acid. To the
flask 8.5 mL of thionyl chloride was added in small portions
with constant shaking. One or two drops of dry DMF were also
added. Reaction mixture was refluxed on water-bath for 2 h.
The excess of thionyl chloride was distilled off. Chloroacetyl
chloride thus obtained is highly fumming and is immediately
used for next step.
65 %; m.f. C16
10 3 2
H O N S required (%): C = 61.94, H = 6.23, N
= 9.03, S = 10.32; Found (%): C = 61.93, H = 6.21, N = 9.01
-
1
and S = 10.29. IR (KBr, nmax, cm ) and PMR DMSO-d (d)
6
Synthesis of 6-chloroacetyl-2-furylchromone (3): 1.272
g (6 mmol) of 2-furylchromone and 0.678 g [6 mmol, 48 mL]
conformed with compound 5 obtained by Hantzsch thiazole
method.
of chloroaetyl chloride as well as 40 mL of CS
a 100 mL round bottom flask. To it was added 1 g of anhydrous
AlCl in portions with shaking. This reaction mixture was
refluxed on water bath for 4 h. CS was distilled off. Now reaction
2
were taken in
RESULTS AND DISCUSSION
3
Prompted by the fact that thiazoles and chromones are of
immense medicinal value and from 2-aminothiazoles a number
of medicinally active compounds come into existence, 6-[2-
aminothiazol-4-yl]-2-furylchromone was synthesised green
chemically by Hantzsch thiazole method (without bromine)
2
mixture was cooled and poured on crushed ice containing HCl.
Solid was allowed to separate and was filtered, washed with
water and recrystallized with ethanol. m.p. = 207-208 ºC, yield
=
75 %, M.F. C15
Found (%) : C = 62.25, H = 3.10. IR (KBr, nmax, cm ): 1690
C=O, str. -COCH Cl], 1640 [C=O str. chromone], 750 [C-Cl
str. -COCH Cl], PMR[CDCl ]: δ 4.66 [s, 2H, -CH protons of
COCH Cl], 6.91 [s, 1H, C -H of chromone], 7.20-7.53 [m, 4H,
protons of furyl ring and C -H of chromone], 7.71 [dd, 1H, C -H
of chromone] 8.21 [d, 1H, C -H of chromone].
9 4
H O Cl required %: C = 62.39, H = 3.12.
-1
21
and King's procedure . 2-Furylchromone (2) was used as
[
2
starting material which was prepared from chalcone (1) obtained
by condensing o-hydroxy acetophenone with furfural in basic
medium and alcoholic solution followed by cyclization of
chalcone with iodine in DMSO. 2-Furylchromone upon Friedel-
Craft reaction with chloroacetyl chloride yielded 6-chloro-
acetyl-2-furylchromone (3). Compound 3 in its IR-spectrum
showed characteristic bands for C=O str. of chromone and
2
3
2
-
2
3
8
7
5
Synthesis of 6-[2-aminothiazol-4-yl]-2-furylchromone
4) (Hantzsch method without bromine):A mixture of 0.2885
(
-1
g [1 mmol] of 3 and 0.076 g [1 mmol] of thiourea in 10 mL of
alcohol was refluxed for 5 h. Solid separated on cooling was
filtered and crystallized from ethanol. m.p. = 319-320 ºC; yield
-COCH
2
Cl side chain at 1640 and 1690 cm , respectively in
Cl in this
compound appeared at 750 cm . PMR spectrum of this com-
pound in CDCl showed -COCH Cl protons at δ 4.66 as singlet.
Other protons showed up in aromatic region. Signal at δ 6.91
can be assigned to C -H of chromone. C -H of chromone and
three protons of furan ring appeared from δ 7.20 to 7.53 as
multiplet. C -H of chromone is assignable to δ 7.71 doublet of
doublet. Whereas, last signal at δ 8.21 which appeared as
doublet can be safely assigned to C -H of chromone.
addition to the usual bands. C-Cl str. of -COCH
2
-1
=
72 %; M.F. C16
H
10
O
3
2
N S requires (%): C = 61.94, H = 6.23,
3
2
N = 9.03, S = 10.32; Found (%): C = 61.98, H = 6.22, N =
-
1
9
.02, S = 10.30; IR (KBr, nmax, cm ): 3400 and 3309 [-NH str.
of -NH group], 1640 [C=O str. of chromone], 2367 [-N=C-S-
str. of thiazole] PMR [DMSO-d ]: δ 2.50 [s, 2H, -NH protons
on thiazole], 6.80-7.40 [m, 4H, C -H of chromone, C -H C -H
-H of furyl ring], 7.50-7.69 [m, 2H, C -H of chromone
-H of chromone], 8.05
3
8
2
6
2
7
3
3
4
and C
5
5
8
5
and C
-H of thiazole], 7.84 [dd, 1H, C
-H of chromone].
Synthesis of 6-acetyl-2-furylchromone (5): 2.12 g [10
mmol] of 2-furylchromone and 1.33 g [15 mmol] of powdered
Anh. AlCl were mixed together in 50 mL of CS in 100 mL
round bottom flask. 1 mL of CH COCl was added dropwise
to the mixture. The mixture was refluxed on water bath for an
hour. CS was distilled off and remaining solid was dropped
7
Compound 3 upon condensation with thiourea in alcoholic
solution afforded 6-[2-aminothiazol-4-yl]-2-furylchromone
(4). Compound (5) in its IR-spectrum predicted its formation
[d, 1H, C
5
-1
-1
2
as -COCH Cl str. at 1690 cm [C=O str.] and 750 cm [C-Cl
str] which were present in IR-spectrum of 3 are absent in it.
3
2
Formation of 2-aminothiazole moiety is concluded by the fact
3
-1
that 2-NH stretching peaks appeared at 3400 and 3309 cm
[symmetric and asymmetric stretchings] and -N=C-S- str. of
2
-1
into chilled water. Solid product was separated by filtration
and recrystallized from ethanol. m.p. = 162-164 ºC; yield =
thiazole at 2367 cm appeared in the IR-spectrum of 4. PMR-
spectrum fully advocated its formation. Compound 4 in its
PMR-spectrum run in DMSO-d
7
0 %; M.F. C15
%): C = 70.83 and H = 3.93. IR (KBr, nmax, cm ): 1680 [C=O
str. -COCH ], 1640 [C=O str. of chromone]. PMR [CDCl
d): 2.68 [s, 3H, -COCH ], 6.61-6.76 [m, 2H, C -H of furan
-H of chromone ring], 7.73-7.70 [m, 3H, C
-H of Chromone ring], 8.40-8.43 [dd, 1H, C
of chromone] and 8.84 [d, 1H, C -H of chromone].
H
10
O
4
requires (%): C = 70.86, H = 3.94; Found
6
showed signals for all the
-1
(
ten protons. Starting from highest field two proton singlet for
3
]
C
2
-NH
2
of thiazole appeared at d2.50. At 6.80-7.40 appeared
-H, C -H and C -H of furan ring.
-H of
-H of thiazole rings. Signal (doublet of
doublet) at d 7.84 was for C -H of chromone and 8.05 doublet
for C -H of chromone completed the proton count.
In other method 4 was synthesised through 6-acetyl-2-
3
(
3
4
C
3
-H of chromone and C
3
4
5
and C
3
3
-H and C
5
-H
-H
Other signals at d 7.50 to 7.69 are assignable to C
chromone and C
8
of furan and C
8
7
5
5
7
Synthesis of 6-[2-aminothiazol-4-yl]-2-furylchromone
by King's procedure: An intimate mixture of 0.254 g [1 mmol]
of 5, 0.152 g [2 mmol] of thiourea and 0.254 g [1 mmol] of
iodine was heated on water-bath under solvent free condition
for 24 h. The reaction mixture was then washed with ether to
5
21
furylchromone (5) by using King's procedure . Compound 5
was synthesised from 2-furylchromone (2) through Friedel-Craft
acylation using acetyl chloride as acylating agent. Structure

Vol. 26, No. 13 (2014)
Green Synthesis of 6-[2-Aminothiazol-4-yl]-2-furylchromone 3991
of 5 was confirmed on the basis of elemental analysis IR and
PMR spectral data. This compound in its IR-spectrum exhibited
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3
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1
1
1
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1
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(
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Out of two green chemical methods of synthesis of title
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effective.
1
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ACKNOWLEDGEMENTS
Research grant by UGC, New Delhi through minor research
project and J.R.F. awarded by CSIR to R.K. are thankfully
acknowledged.