An efficient solid-phase green synthesis of chromen-2-one derivatives

Article abstract of DOI:10.14233/ajchem.2013.15055

An efficient route for the synthesis of chromen-2-one derivatives (3a-h) via Knoevenagel condensation under solid phase by the condensation of salicylaldehydes (1) with various ethyl acetate derivatives (2) is described. The reaction has been done under conventional method as well as under solid-phase method. The later method has been found to be much better in terms of time and yield. The structures of all the compounds were confirmed by spectral and analytical data.

Full text of DOI:10.14233/ajchem.2013.15055

Asian Journal of Chemistry; Vol. 25, No. 12 (2013), 6885-6887
http://dx.doi.org/10.14233/ajchem.2013.15055
An Efficient Solid-Phase Green Synthesis of Chromen-2-one Derivatives
1
,*
1
2
S. TASQEERUDDIN , ABDULLAH S. AL-ARIFI and P.K. DUBEY
1
2
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
Department of Chemistry, Jawaharlal Nehru Technological University, College of Engineering, Kukatpally, Hyderabad-500 085, India
*
Corresponding author: E-mail: tasqeeruddin@gmail.com
Received: 31 December 2012;
(
Accepted: 5 June 2013)
AJC-13594
An efficient route for the synthesis of chromen-2-one derivatives (3a-h) via Knoevenagel condensation under solid phase by the condensation
of salicylaldehydes (1) with various ethyl acetate derivatives (2) is described. The reaction has been done under conventional method as
well as under solid-phase method. The later method has been found to be much better in terms of time and yield. The structures of all the
compounds were confirmed by spectral and analytical data.
Key Words: Salicylaldehyde, Various derivatives of ethyl acetate, ZrOCl
2 2
.8H O (10 mol %), Mortar and pestle.
1
phase. H NMR was recorded on VARIAN 400 MHz instru-
ment and Mass spectra were recorded on Agilent-LC-MS
instrument.
INTRODUCTION
The preparation and screening of small molecules libraries
1
based on natural products have attracted in recent years .
Synthesis of 3 (conventional method): A mixture of 1
Chromen-2-ones (2H-1-benzopyran-2-ones) are well-known
2
structural unit present in several natural products . Chromen-
(
2 2
3 mmol), 2 (3 mmol) and ZrOCl .8H O (10 mol %) was heated
under neat conditions for 0.5 h. The reaction was monitored
by TLC. After the complete disappearance of the starting
material spot on TLC, the reaction mixture was cooled to room
temperature and poured in to ice-cold water (100 mL). The
separated solid was filtered, thoroughly washed with water
and dried to obtain the crude product. The latter was recrys-
tallized from ethanol to yield pure 3.
3
-one derivatives have been used as therapeutic agents , optical
2
4
5
bleaching agents and active media for tunable dye lasers . In
view of the above observations and in continuation of our
studies in the field of oxygen heterocycles, the present investi-
gation deals the synthesis of chromen-2-one derivatives.
Various methods are known for the synthesis of substi-
6
tuted chromen-2-ones in the literature including the Pechmann ,
Compound 3a. Yellow solid; m.p. 119-121 ºC;
Compound 3b. Yellow solid; m.p. 91-92 ºC; IR (KBr):
7
8
9
10
Perkin , Knoevenagel , Claisen , Reformatsky and Wittig
11
reactions . Chromen-2-ones have been synthesized by the
Kostanecki-Robinson reaction of o-hydroxyarylalkyl ketones
with acid anhydrides, which proceeds through an ester enolate
-1
722 cm (strong, sharp, -CO- of coumarin ring), 1662 cm
-1
1
1
); H NMR (DMSO-d
(strong, sharp, CO of COOC
H
2 5
6
/TMS)
δ: 1.43 (t, 3H, CH ), 4.43 (q, 2H, CH
3
2
), 7.39-8.58 (complex, m,
12
intermediate . Most of the procedures suffer from several
disadvantages like harsh reaction conditions, such as the use
of stoichiometric amount of minerals, Lewis acids or toxic
reagents, often under high temperatures and with longer
.+
H aryl protons); MS: m/z = 218 (M +1): Elemental analysis
5
(%): found C 66.17, H 4.49; C12
H
10
O
4
requires C 66.05, H 4.58.
Compound 3c.Yellow solid; m.p. 159-161 ºC; IR (KBr):
-1
-1
724 cm (strong, sharp, -CO- of coumarin ring), 1656 cm
1
13
reactions time, poor substituent tolerance and low yields .
Thus, it is clearly evident that development of new and flexible
protocols is required.
1
); H NMR (DMSO-d
(strong, sharp, CO of COCH
3
6
/TMS): δ
2
1
.52 (s, 3H, -CH
3
), 7.33-8.55 (complex, m, 4H aryl protons),
.+
1.7 (s, 1H, D O exchangeable -OH); MS: m/z = 205 (M +1).
2
Elemental analysis (%): found C 66.17, H 4.49; C12
requires C 66.05, H 4.58.
Compound 3d. Yellow solid; m.p. 97-98 ºC; IR (KBr):
10 4
H O
EXPERIMENTAL
Melting points are uncorrected and were determined in
open capillary tubes in sulphuric acid bath. TLC was performed
on silica gel-G and spotting was done using UV-light. IR spectra
were recorded with Perkin- Elmer 1000 instrument in KBr
-1
-1
1728 cm (strong, sharp, -CO- of coumarin ring), 1668 cm
1
); H NMR (DMSO-d
(strong, sharp, CO of COOC
H
2 5
6
/TMS)
3 2
δ: 1.55 (t, 3H, CH ), 4.31 (q, 2H, CH ), 7.27-8.42 (complex,

6
886 Tasqeeruddin et al.
Asian J. Chem.
m, 4H aryl protons), 11.7 (s, 1H, D
2
O exchangeable -OH);
2.55 (s, 3H, -CH ), 7.34-8.44 (complex, m, 3H, aryl protons);
3
.+
MS: m/z = 255 (M + 1). Elemental analysis (%): found C 51.39,
.+
MS: m/z = 234 (M + 1). Elemental analysis (%): found C
60.59, H 4.27; C12
H
10
O
5
requires C 61.54, H 4.30.
6 3 2
H 2.35, Cl 27.58; C11H O Cl requires C 50.90, H 2.2, Cl 26.98.
Compound 3e.Yellow solid; m.p. 139-140 ºC; IR (KBr):
Compound 3h.Yellow solid; m.p. 131-133 ºC; IR (KBr):
-1
-1
-1
1735 cm (strong, sharp, -CO- of coumarin ring), 1670 cm
1
732 cm (strong, sharp, CO of coumarin ring), 1660 (strong,
1
1
sharp, CO of COCH
H, -CH ), 3.88 (s, 3H, -OCH
aryl protons); MS: m/z = 218 (M +1). Elemental analysis (%):
found C 65.02, H 4.58; C12 requires C 66.05, H 4.62.
Compound 3f. Yellow solid; m.p. 89-91 ºC; IR (KBr):
3
); H NMR (DMSO-d
6
/TMS): δ 2.68 (s,
(strong, sharp, CO of COOC
δ : 1.51 (t, 3H, CH
m, 3H aryl protons); MS: m/z = 285 (M +1). Elemental analysis
2
H
5
); H NMR (DMSO-d
6
/TMS)
3
3
3
), 7.38-8.48 (complex, m, 4H,
3
), 4.31 (q, 2H, CH
2
), 7.27-8.41 (complex,
.+
.+
H
10
O
4
(%): found C 50.20, H 2.81, Cl 24.70; C12
49.90, H 2.77, Cl 23.88.
8 4 2
H O Cl requires C
-1
-1
1
731 cm (strong, sharp, -CO- of coumarin ring), 1655 cm
1
); H NMR (DMSO-d
Alternative general procedure for the preparation of
3 (solid-phase grinding method): In the solid-phase synthesis
(strong, sharp, CO of COOC
δ: 1.55 (t, 3H, CH
2
H
5
6
/TMS)
),
1
method 3a (i.e., 3, R = R = R = H), has been synthesized.
2
3
3
), 3.80 (s, 3H, -OCH ), 4.29 (q, 2H, CH
3
2
.+
1a
1
2
Thus, when equimolar quantities of (i.e., 1, R = R = H) and
7
.23-8.38 (complex, m, 4H aryl protons); MS: m/z = 248 (M
3
+
1). Elemental analysis (%): found C 61.88, H 4.66; C13
H O
12 5
2 2
2a (i.e., 2, R = H) were ground along with ZrOCl ·8H O (10
requires C 62.90, H 4.87.
Compound 3g. Yellow solid; m.p. 151-53 ºC; IR (KBr):
mol %) in a mortar with the help of pestle at room temperature,
the reaction was completed within 13 min as shown by TLC
analysis of crude mixtures. The mp and the spectral data of
the obtained product were coincided with 3a.
-1
1
742 cm (strong, sharp, CO of coumarin ring) 1662 (strong,
1
3 6
sharp, CO group of COCH ); H NMR (DMSO-d /TMS): δ
TABLE-1
PHYSICAL DATA OF COMPOUNDS (3a-h)
S.
No.
Substrates
1
Products
Method-A
Time (min) Yield (%)
Method-B
2
Time (min)
Yield (%)
92
a
O
30
86
13
OH
O
O
O
C OC H5
C CH3
O
2
H C
2
CH3
H
C
O
OH
b
O
60
84
30
91
O
O
C OC H5
C OC H5
2
H C
2
OC H
2
5
2
H
C
O
O
O
c
O
O
O
40
90
81
82
20
30
93
90
OH
C OC H5
C CH3
2
H C
CH3
2
H
HO
HO
C
HO
O
O
OH
O
d
O
O
O
2
C OC H5
C OC H5
OC H
H C
2
5
2
HO
H
C
O
2
O
O
e
f
OH
O
O
O
30
90
45
83
81
84
15
40
20
92
94
92
O
C OC H5
C CH3
2
H2C
CH3
H
H CO
3
C
O
H CO
3
O
O
OH
O
O
2
C OC H5
C OC H5
OC2H5
H
H2C
H3CO
H CO
3
C
O
2
O
O
O
g
Cl
O
O
Cl
OH
C OC H5
C CH3
2
H C
CH3
2
H
Cl
Cl
Cl
C
O
O
O
h
O
Cl
O
O
O
60
80
40
90
OH
C OC H5
C OC H5
2
H C
OC2H5
2
Cl
2
H
Cl
C
O
O
Method-A is conventional method & Method-B is Physical grinding method

Vol. 25, No. 12 (2013)
RESULTS AND DISCUSSION
An Efficient Solid-Phase Green Synthesis of Chromen-2-one Derivatives 6887
Method-A
R2
R1
OH
O
R2
R1
O
O
C OC
2
H
5
1
Salicylaldehyde (1a, i.e., 1, R = R = H) on heating with
2
H
2
C
3
H
R
C
O
R3
3
ethyl acetate (2a, i.e., 2, R = COCH
Method-B
) and ZrOCl ·8H
3 2
2
O (10
(
1
)
(
2
)
( )
3
Substituted
salicylaldehyde
Ethyl acetate
mol %) for 0.5 h, gave the previously reported 3-acetylchromen-
1
2
3
14
2
3
-one (3a, i.e., 3, R = R = H, R = COCH ) homogenous on
Scheme-I
TLC and different from the starting material. The structure of
this compound was supported by spectral and analytical data.
Method-A is conventional
Method-B is solid-phase grinding
-1
Thus, its IR (KBr): 1725 cm (strong, sharp, -CO- of coumarin
1
-
ring), 1668 cm (strong, sharp, CO of COCH
1
1
R = R = H, OH, OCH
2
3
); H NMR
3
, Cl.
2
R = Cl,
3
R = COCH
(
DMSO-d /TMS) δ: 2.77 (S, 3H, CH ), 7.19-8.88 (complex,
3
6
m, 5H aryl protons); Its mass spectrum when recorded in CI
+
method showed a molecular ion peak at m/z (i.e., M. +1) 188
3 2 5
, COOC H .
(
base peak) corresponding to a molecular mass of 187
Scheme-1).
By adopting the same procedure, other compounds
ACKNOWLEDGEMENTS
(
This project was supported by King Saud University,
Deanship of Scientific Research, College of Science Research
Center.
namely ethyl 2-oxo-2H-chromene-3-carboxylate (3b, i.e., 3,
1
R , R = H, R = COC H ), 3-acetyl-6-hydroxy-2H-chromen-
2 5
2
3
1
-one (3c, i.e., 3, R = OH, R = H, R = COCH
2
3
2
3
), ethyl 6-
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2
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3 3
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2
3
3
a (i.e., 3, R = R = H, R = COCH ) could also be prepared
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1
by an alternative method. Thus 1a (i.e., 1, R = R = H) and 2a
2
1
3
i.e., 2, R = COCH
(
3
) were ground in mortar with the help of
3
pestle in the presence of ZrOCl .8H O (10 mol %) at room
2
2
1
temperature. The product obtained on processing the solid
reaction mixture was found to be identical in all respects (m.p.,
m.m.p. and co-TLC analysis) with 3a obtained earlier above
Scheme-I. The results are summarized inTable-1.A comparison
between the two methods shows that in the physical grinding
technique the time is drastically reduced and the yields are
comparable.
(
1
1
1
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