Hydromagnesite as an efficient recyclable heterogeneous solid base catalyst for the synthesis of flavanones, flavonols and 1,4-dihydropyridines in water

Article abstract of DOI:10.1002/adsc.201300555

A form of hydromagnesite (HM) with flower-like thin-sheet morphology was synthesized by an environmentally benign approach using simple conventional heating at moderate temperature without using any template in water as medium. The versatility of this HM catalyst was studied in the synthesis of flavanones, flavonols and the multicomponent synthesis of 1,4-dihydropyridines in water. The recyclability of catalyst was studied for six times and there was no appreciable loss in its catalytic activity. Copyright

Full text of DOI:10.1002/adsc.201300555

FULL PAPERS
DOI: 10.1002/adsc.201300555
Hydromagnesite as an Efficient Recyclable Heterogeneous Solid
Base Catalyst for the Synthesis of Flavanones, Flavonols and
1,4-Dihydropyridines in Water
U. Chinna Rajesh,a Sunny Manohar,a and Diwan S. Rawata,*
a
Department of Chemistry, University of Delhi, Delhi – 110007, India
Fax : (+91)-11-2766-7501; phone: (+91)-11-2766-2683; e-mail: dsrawat@chemistry.du.ac.in
Received: June 22, 2013; Published online: October 9, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300555.
Abstract: A form of hydromagnesite (HM) with synthesis of 1,4-dihydropyridines in water. The recy-
flower-like thin-sheet morphology was synthesized clability of catalyst was studied for six times and
by an environmentally benign approach using simple there was no appreciable loss in its catalytic activity.
conventional heating at moderate temperature with-
out using any template in water as medium. The ver- Keywords: 1,4-dihydropyridines; flavonols; flava-
satility of this HM catalyst was studied in the synthe- nones; heterogeneous solid base catalyst; hydromag-
sis of flavanones, flavonols and the multicomponent nesite
Introduction
This prompted us to study the catalytic potential of
hydromagnesite, which has found applications in
Although many organic reactions can be promoted by rubber, plastic and fire retardant industries,[7] but the
homogeneous or heterogeneous catalysis, the later catalytic potential was seldom examined. Hydromag-
method offers many advantages such as easy work-up, nesite, the precursor of MgO, is a hydrated basic
recyclability and less waste production.[1] The global magnesium carbonate mineral with the formula
concern about the climate change, energy production Mg5ACHTNUGTRNE(NUG CO3)4(OH)2·4H2O, it has a three-dimensional
and conservation has prompted scientists to develop framework of MgO6 octahedra and triangles of car-
novel heterogeneous catalysts for industrial processes. bonate ions (Figure 1).[8] It is the only species which is
The development of solid base catalysts for an envi- stable under atmospheric conditions among the six
ronmentally friendly synthesis of fine chemical or or- known magnesium carbonates found in nature, the
ganic intermediates is an important research topic for other five being magnesite (MgCO3), nesquehonite
the green and sustainable society. The ultimate goal
of heterogeneous catalysis must be 100% product se-
lectivity, which eliminates the unwanted side products
and allows the process to be greener. Among the het-
erogeneous catalysts, nano-structured inorganic mate-
rials have received considerable attention and it has
been well established that, depending on the shape
and size of the pores, these materials can exhibit dif-
ferent activities in organic reactions.[2] Magnesium
oxide is one such inorganic material, which has been
employed as a heterogeneous catalyst in various or-
ganic reactions.[3] Magnesium oxide is prepared from
hydromagnesite at very high temperature (>4508C)
and it releases carbon dioxide which makes this pro-
cess environmentally unfriendly.[4–6] In addition, MgO-
catalyzed reactions generally require longer reaction
times and toxic organic solvents which limits their ef-
ficacy towards greener methodologies.
Figure 1. General representation of the surface of hydro-
magnesite (striped part represents the MgO6 octahedra in
a three-dimensional arrangement[8]).
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Hydromagnesite as an Efficient Recyclable Heterogeneous Solid Base Catalyst
(MgCO3·3H2O), lansfordite (MgCO3·5H2O), artinite Results and Discussion
[MgCO3·Mg(OH)2·3H2O],
and
dypingite
[4MgCO3·Mg(OH)2·5H2O).[8]
Preparation and Characterization of the Catalyst
Several groups have reported the synthesis of dif-
ferent morphological forms of hydromagnesite during Hydromagnesite was prepared as described in the Ex-
the preparation of MgO.[4,5] There are only two re- perimental Section and characterized by the powder
ports on the catalytic activity of hydromagnesite: Dai X-ray diffraction technique. The pattern could be in-
et al. reported hydromagnesite as an effective catalyst dexed in monoclinic symmetry (space group p2/c)
in the Baeyer–Villiger oxidation of cyclohexanone with refined lattice parameters of a=10.0451(2), b=
and, more recently, Ebitani et al. reported that the co- 8.9046(6), c=8.3542(3) ꢁ and b=1148C. The average
existent hydromagnesite increased the catalytic activi- crystallite size is 20 nm as estimated by the Scherrer
ty of hydrotalcite catalyst for transesterifications of analysis. All the reflections matched well with the re-
glycols into cyclic carbonates.[9,10] Taking account of ported ones (JCPDS File No: 25-513) (Figure 2a).[4]
these observations, and in continuation of our work The lattice parameters were obtained from the Le-
on developing novel recyclable heterogeneous cata- bail fitting of the X-ray diffraction pattern using the
lysts for the synthesis of bioactive molecules,[11] we an- program Full Prof suite (Figure 2b).[15]
ticipated that hydromagnesite could be used as better
The surface morphology of HM was revealed as
single site catalyst over MgO in water medium due to a flower-like arrangement of sheets (Figure 3), which
the presence of basic and hydrophilic OHÀ, HCO3
was further supported by the transmission electron
À
groups on its surface.[9] We report herein the synthesis microscopy (TEM) images as shown in Figure 2c. The
of hydromagnesite (HM) with a flower-like sheet
morphology by a modified literature method[4] and its
catalytic potential in the synthesis of medicinally im-
portant flavanones, flavonols and 1,4-dihydropyridines
in aqueous media. Flavanones and flavonols belong to
a class of flavonoid natural products which exhibit
various biological properties including anticancer, an-
tibacterial, antifungal, antileishmanial, antitrypanoso-
mal, antioxidant and a-glucosidase inhibitory activi-
ties.[12]
In general, flavanones have been synthesized under
homogeneous conditions using Ca(OH)2, KOH,
NaOH, piperidine, K2CO3, proline, H2SO4, H3PO4
etc., and heterogeneous catalysts such as hydrotal-
cites, zeolites, silica hydroxyapatite, MgO, KF/natural
phosphate, alumina supported CeCl3·7H2O, NaI
etc.[13] There have been limited reports found on the
synthesis of 2,3-dihydroflavonol.[14] However, the con-
version of chalcone into flavanone and 2,3-dihydro-
ACHTUNGTRENNUNGflavonol has limitations such as low conversion, high
temperature, toxic organic solvents, non-recyclable
catalysts and usage of additives etc. In contrast, hy-
dromagnesite as catalyst has become increasingly ap-
pealing because of its affordability, low toxicity,
greener, sustainable and environmentally benign
nature and which, in addition, explores the superior
catalytic activity as a novel solid base catalyst.
To the best of our knowledge this is the first report
on the synthesis of a flower-like thin-sheet morpholo-
gy of hydromagnesite and its catalytic application in
the synthesis of flavanones, flavonols and 1,4-dihydro-
pyridines in aqueous medium. This opens up a new
direction for the exploration of the catalytic potential
of the hydromagnesite, a precursor of magnesium
oxide, a well-known catalyst for many organic trans-
formations.
Figure 2. (a) PXRD and (b) Le Bail fitting of PXRD; (c)
TEM and (d) SAED images of hydromagnesite.
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U. Chinna Rajesh et al.
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Figure 3. (a) and (b) SEM images of hydromagnesite.
higher intense peaks in the powder XRD pattern indi-
cate the high crystallinity of the prepared hydromag-
nesite material (Figure 2). Morever, it was further
supported by the selected area electron diffraction
(SAED) image (Figure 2d and see the Supporting In-
formation for the EDX pattern of HM).
Figure 5. TGA of hydromagnesite.
The BET surface area and pore volume of HM
were calculated, and found to be 45.5 m2 gÀ1 and
The first weight loss (17.8%) was attributed to the
0.15 cm3 gÀ1, respectively. The concentration of basic dehydration of crystalline water and dehydroxylation
sites of HM was calculated using titration method, process at 100–2808C, and the second weight loss
and found to be 21.7 mmolgÀ1.
(37.9%) was due to the evolution of CO2 at 280–
The room temperature FT-IR spectrum (Figure 4) 4808C. The total weight loss in both the steps is
shows the asymmetric stretching vibration of carbon- summed up to 55.7%, which is close to a predicted
ate ion split into two bands at 1485 and 1420 cmÀ1 (n3 theoretical weight loss of 56.7% for the stoichiometric
mode). In addition the characteristic crystalline water conversion of hydromagnesite to MgO.[16]
is observed as strong bands at 3524 and 3453 cmÀ1.
Initially, the catalytic potential of as synthesized
À
Moreover, an almost free O H symmetric stretching HM material was studied as a heterogeneous solid
vibration band is seen at 3650 cmÀ1 and all the other base catalyst in the synthesis of flavanones through
bands are in good agreement with the reported intramolecular oxa-Michael addition involving cycli-
data.[4]
zation of 2’-hydroxychalcones (Scheme 1). The reac-
The thermal decomposition study of HM was stud- tion worked best when HM was taken as catalyst and
ied by using TGA analysis under an N2 atmosphere as water as solvent.
shown in Figure 5.
Scheme 1.
For the preliminary study and optimization of the
reaction conditions involving flavanones (2), we stud-
ied the intramolecular oxa-Michael cyclization of 2’-
hydroxychalcone (1a) in the presence of hydromagne-
site as a catalyst. At first, the reaction was carried out
in the presence of various dry organic solvents under
conventional heating, generally at their reflux temper-
atures. This afforded the flavanone 2a in poor to mod-
erate yields as shown in Table 1.
Interestingly, excellent results were obtained when
the cyclization was performed in water as a solvent at
reflux temperature, which afforded the product in
85% isolated yield and it was observed that yield of
Figure 4. FT-IR of hydromagnesite.
the product 2a drops significantly at lower tempera-
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Hydromagnesite as an Efficient Recyclable Heterogeneous Solid Base Catalyst
Table 1. Optimization of the reaction conditions for the syn-
thesis of flavanone 2a under conventional heating.[a]
These optimized conditions were further used to
explore the generality of the reaction and a series of
flavanones bearing electron-donating and electron-
withdrawing substituents on the phenyl ring were syn-
thesized (Table 2, 2a–2n). The study revealed that the
electron-withdrawing substituents enhanced the rate
of reaction and gave good isolated yield (2b–2d).
Moreover, the presence of halogens (chloro, bromo
and fluoro) at the para position of the benzene ring
gave moderate yields of 50–68% (2j, 2k and 2m). On
the other hand, chloro substitution at the meta posi-
tion improved the yield to 75% (2l). As soon as they
were replaced with electron-donating groups like Me,
i-Pr, t-Bu (Table 2, 2e–2g) yields dropped significantly
from 65 to 55%. Also, the presence of a strong elec-
tron-donating group like methoxy at the para position
gave a moderate yield, whereas such substitution at
the meta position improved the yield (Table 2, 2h and
2i).
Entry Solvent
Temp. [oC] Time [h] Yield[b] [%]
1
2
3
4
5
6
7
8
tetrahydrofuran 75
5
5
5
5
4
2
2
2
3
3
3
3
3
10
30
32
36
45
70
73
65
45
85
35
20
–
toluene
110
90
110
65
acetonitrile
1,4-dioxane
acetone
PEG-400
PEG-600
120
120
ethylene glycol 120
9
ethanol
water
water
water
water
85
100
70
50
25
10
11
12
13
Next, we studied the comparative catalytic activity
of HM with other commercially available base cata-
lysts under our optimized conditions and found that
HM was the most suitable catalyst that can be em-
ployed for this reaction The reactions with other base
catalyst gave poor yields (Table 3, entries 2 to 7) and
in the presence of Lewis acid catalysts either trace
[a]
Reaction conditions: 2-hydroxychalcone (1 mmol), HM
catalyst (50 mol%) in 3 mL of solvent, reflux conditions.
Isolated yield.
[b]
ture and no product formation was observed at room amounts or no product formation was observed. With-
temperature (Table 1, entries 10–13). The optimiza- out catalyst, the reaction did not proceed even after
tion and standardization of reaction conditions re- a prolonged time under the optimized conditions.
vealed that HM (50 mol%) as a catalyst, in water as This gives an insight that addition of catalyst is crucial
solvent at 1008C are the optimum conditions for the for driving the course of the reaction.
preparation of these biologically active molecules (see
In order to further explore the catalytic activity of
the Supporting Information for a catalyst loading hydromagnesite, we studied this catalyst for the syn-
study).
Table 2. Hydromagnesite-catalyzed intramolecular oxa-Michael addition of 2-hydroxychalcones (1a–n) to afford flavanones
(2a–n) at 1008C in water as solvent.[a]
Compound
Ar
Time [h]
Conversion[b] [%]
Yield[c] [%]
Observed mp [oC]
Lit. mp [oC]
2a
2b[d]
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
C6H5
3-C5H4N
3
3
3
3
4
4
4
4
3
5
5
4
5
4
94
96
90
97
73
70
63
72
88
62
76
84
60
72
85
88
84
93
65
60
55
65
83
53
68
75
50
60
78–79
liquid
123–125
155–157
69–70
75–76
105–107
95–96
78–79
79–80
77–78[17]
unknown
121–122[22]
156–157[22]
68–70[17]
76–77[18]
104[19]
2-NO2C6H4
4-NO2C6H4
4-MeC6H4
4-i-PrC6H4
4-t-BuC6H4
4-MeOC6H4
3-MeOC6H4
4-FC6H4
4-ClC6H4
3-ClC6H4
4-BrC6H4
piperonyl
95–97[17]
79–80[17]
78–79[20]
84–85[17]
97–99[21]
117[17]
83–85
96–98
118–119
124–126
125–126[17]
[a]
Reaction conditions: 2-hydroxychalcone (1 mmol), HM catalyst (50 mol%) in 3 mL of solvent, reflux conditions.
Conversion was determined by H NMR spectroscopy of the crude reaction mixture.
Yield refer to isolated pure products.
Compound 2b is a liquid.
[b]
[c]
[d]
1
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Table 3. Role of the catalyst in the synthesis of flavanone 2a
in water.[a]
Entry
Catalyst[b]
HM
Yield[c] [%]
1
85
2
G
40
3
4
Mg(OH)2
MgO
38
45
5
CaO
30
6
7
K2CO3
Al2O3
45
20
8
I2
trace
9
FeCl3
trace
10
11
BF3·OEt2
no catalyst
no reaction
no reaction
[a]
Reaction conditions: 2-hydroxychalcone (1 mmol), HM
catalyst (50 mol%) in 3 mL of water, reflux conditions.
All are commercially available bulk materials except for
HM (hydromagnesite with flower-like sheet morpholo-
gy).
[b]
[c]
Figure 6. Comparative study of hydromagnesite flower-like
sheets (HM) with other magnesium-based catalysts in the
Isolated yield of pure products.
[a]
synthesis of flavanone 2a under our optimized conditions.
Hydromagnesite flower-like sheet (HM, BET: 45.5 m2gÀ1);
C-HM=[(MgCO3)4·Mg(OH)2·5H2O; BET: 10.3 m2gÀ1], C-
Mg(OH)2 (BET: 12 m2gÀ1) and C-MgO (BET: 14.5 m2gÀ1)
are commercially available bulk materials.
Table 4. Role of the solvent for the HM-catalyzed synthesis
of 2,3-dihydroflavonol (3).[a]
Scheme 2.
Entry
Solvent
Temp. [oC]
Time [h]
Yield[b] [%]
1
2
3
4
5
6
7
ethanol
acetone
PEG-400
PEG-600
glycerol
water
80
65
80
80
80
80
25
4
4
4
4
3
2
6
60
50
48
55
62
75
–
thesis of 2, 3-dihydroflavonol (3) starting from com-
pound 1a (Scheme 2).
It was found that a 30% aqueous solution of H2O2
and hydromagnesite (50 mol%) as a catalyst at a tem-
perature of 808C in water as solvent were the opti-
mum conditions (see the Supporting Information for
a catalyst loading study) and led to the desired prod-
uct selectively with good yields (Scheme 2). In order
to get an insight into the mechanism, the samples
were collected from the reaction mixture at different
water
[a]
Reaction conditions: 2-hydroxychalcone (1 mmol), HM
catalyst (30 mol%), 30% H2O2 (0.6 mL) in 3 mL of sol-
vent at 808C.
[b]
Isolated yield.
1
time intervals and analyzed by H NMR spectroscopy,
no peaks were observed corresponding to an epoxide
intermediate. This gives a clear idea about the highly comparison with other Mg-based catalysts as shown
reactive and unstable nature of the epoxide inter- in Figure 6.
mediate, and that it cyclized to yield 2,3-dihydro-
ACHTUNGTRENNUNGflavonol (3) (Figure 6).
We found that HM catalyst was far superior to
other Mg-based catalysts and interestingly 75%
Moreover, in order to study the utility of hydrogen flavanACTHUNTGRENNGoU ne formation was observed in 30 min to 1 h
peroxide in the reaction, the effective concentration and finally reached 94% in 3 h. In contrast, in the
of H2O2 was calculated after completion of the reac- presence of other Mg-based catalysts the reaction was
tion and it was observed that approximately 87% of sluggish with poor conversions of about 40–50% in
H2O2 was utilized in the reaction.[23] Table 4 depicts 3 h.
the role of solvent for the optimization of the reaction
To explore the versatility of HM catalyst in water
conditions involving the synthesis of 2,3-dihydro- medium, we studied the multicomponent one-pot syn-
A
thesis of 1,4-dihydropyridines. The four-component
We further investigated the efficacy of HM catalyst Hantzsch reaction provides access to 1,4-dihydropyri-
in terms of the formation of flavanone versus time in dines that are known to have a wide range of biologi-
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Hydromagnesite as an Efficient Recyclable Heterogeneous Solid Base Catalyst
Scheme 3.
cal properties such as antitumour, antidiabetic agents, (Table 5, 7a–7k). Substrates having electron-donating
Alzheimer, vasodilator, antiatherosclerotic, geropro- groups like OMe, Me at para, meta and ortho posi-
tective, hepatoprotective and cardiovascular agents.[24] tions showed more reactivity and gave excellent
The model reaction (Scheme 3) was performed by yields (90–98%) within the time intervals of 20–
condensation of benzaldehyde, 1,3-cyclohexanedione, 35 min (Table 5, 7f–7j). In contrast, those substrates
ethyl acetoacetate, ammonium acetate and HM cata- having electron-withdrawing groups like NO2, Cl at
lyst (30 mol%) in water at 908C for 20 min and gave para, meta and ortho positions showed relatively less
the 1,4-dihydropyridine (7a) with 93% isolated yield reactivity with good yields (80–87%) in 40–45 min
(see Supporting Information for a catalyst loading (Table 5, 7b–7e and 7k).
study).
The possible mechanism for the formation of
The model reaction was also carried out in the ab- flavan
N
flavanone 2a. In a second pathway, H2O2 attacks
Table 5. HM-catalyzed multicomponent synthesis of 1,4-di-
a basic hydroxy or carbonate function on the surface
hydropyridines in water.[a]
of hydromagnesite to form an HOOÀ species,[9,28] and
Com- Ar
pound
Time Yield[b] Observed/Lit
this reacts with the olefinic bond of substrate 1a to
yield the epoxide intermediate III, the isolation of
which from the reaction mixture, is not possible and
a selective intramolecular nucleophilic addition at the
b-position of the epoxide ring yields 2,3-dihydro-
[min] [%]
mp [oC]
7a
7b
7c
7d
7e
7f
7g
7h
7i
C6H5
25
45
45
45
45
20
35
93
80
83
86
87
95
91
94
98
92
85
239–240/240–241[25]
192–194/190–191[25]
201–202/198–200[25]
205–207/204–205[25]
235–237
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
4-ClC6H4
4-MeOC6H4
3-MeOC6H4
3,4-MeO2C6H3 20
3,4,5-MeO3C6H2 20
4-MeC6H4
AHCTUNGTRENNUNG
flavonol (3).[29]
Thus, hydromagnesite with its flower-like sheets, its
192–194/193–195[25]
197–199/unknown
193–195/192–194[26]
182–184/180–182[26]
241–243/241–242[25]
245–247/unknown
defined shape,À size, high surface area and accessible
À
basic HCO3 , OH as well as Lewis acidic Mg2+ sites
allows the chemisorption of substrates on its surface
to evolve the single-site catalyst by the successful
transfer of molecular chemistry to surface metal-or-
ganic chemistry to furnish the corresponding products
selectively.
The recyclability of hydromagnesite catalyst was ex-
amined in the intramolecular oxa-Michael addition of
2-hydroxychalcone (1a) to flavanone (2a) and also in
the synthesis of 3-hydroxyflavanone (3) under the op-
timized conditions. The results show that there is no
loss of catalyst activity even after six cycles as shown
in Figure 8 (see the Supporting Information for SEM
and XRD images of the recycled catalyst). For this re-
cycling study of hydromagnesite catalyst, after each
cycle the catalyst was washed with ethanol and dried
at 808C in an oven.
7j
7k
30
40
2,4-Cl2C6H3
[a]
Aldehyde (1 mmol), 1,3-cyclohexanedione (1 mmol),
ethyl acetoacetate (1 mmol), NH4OAc (1.5 mmol) and
HM catalyst (30 mol%) in water (2 mL) at 908C.
Isolated yield.
[b]
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U. Chinna Rajesh et al.
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Figure 7. Plausible mechanism for the formation of flavanone 2a and 2,3-dihydroflavonol 3.
with good yield. The excellent performance of the hy-
dromagnesite catalyst in water medium may be due
to flower-like thin-sheet morphology with high sur-
face area and also the presence of hydrophilic interac-
À
tions of HCO3 and OHÀ groups on its surface.
Experimental Section
Preparation of the Catalyst
MgCl2·6H2O (3.76 g) was dissolved in 33 mL of freshly pre-
pared urea solution (6M) and mixed with 43 mL of ethylene
glycol in a 100-mL round-bottom flask. The reaction mix-
ture was heated at 1108C for 5 h under continuous stirring
(600 rpm). The precipitated hydromagnesite was collected
by filtration and washed several times with deionized water
followed by final washing with ethanol. The thus obtained
hydromagnesite was dried at 808C for 6 h in oven.
Figure 8. Recycling study of hydromagnesite catalyst for the
synthesis of flavanone 2a.
Characterization
TG-DTA analysis (PerkinElmer, Pyris Diamond) with
a heating rate of 108CminÀ1 in a nitrogen atmosphere was
used to study the thermal decomposition behaviour of the
as-prepared (dried) sample with respect to a-Al2O3 as the
reference. X-ray diffraction (XRD) patterns were recorded
on Rigaku Rotaflex spectrometer at a 2V range of 10–708
with Cu Ka radiation. Specific surface area and pore size
analysis of the samples were measured by nitrogen adsorp-
tion using a sorptometer (ASAP-2010, Micromeritics). The
Conclusions
In conclusion, we have succeeded in the synthesis of
hydromagnesite (HM) with flower-like thin-sheet
morphology as a novel green catalytic system for the
synthesis of biologically active flavanones, flavonol
and 1,4-dihydropyridines in water medium for the
first time. Moreover, the selective conversion of 2-hy-
droxychalcone to 2,4-dihydroflavanol was achieved samples were degassed at 1008C for 3 h prior to measure-
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Hydromagnesite as an Efficient Recyclable Heterogeneous Solid Base Catalyst
ments. Fourier transform infrared (FT-IR) spectra were re-
corded on Perkin-Elmer apparatus and the samples were
prepared by mixing the powdered solids with KBr. Scanning
electron microscopy (SEM) measurements were performed
on a Philips XL30 electron micrograph. Transmission elec-
tron microscopy (TEM), EDX and SAED micrographs
were obtained on a Joel JEM 2010 transmission electron mi-
croscope. The samples were supported on carbon-coated
copper grids for the experiments. Melting points were mea-
sured with a Bꢂchi B-540 melting-point apparatus and are
(KBr): nmax =3462 (OH), 1695 cmÀ1 (C=O); anal. calcd. for
C15H12O3: C 74.99, H 5.03; found: C 74.96, H 5.01.
General Procedure for Synthesis of 1,4-Dihydro-
pyridines (7a–7k)
A mixture of aldehyde (1 mmol), 1,3-cyclohexanedione
(1 mmol), ethyl acetoacetate (1 mmol), ammonium acetate
(1.5 mmol) and HM catalyst (30 mol%) in water (2 mL) was
heated at 908C. After completion of the reaction (as moni-
tored by TLC), organic solvent was added to reaction mix-
ture which was then centrifuged to separate the catalyst.
This procedure was repeated for 3–4 times to extract the
product from the catalyst surface. The combined organic
layers were dried over Na2SO4 and the solvent was removed
under reduced pressure. Recrystallization of crude product
from hot ethanol gave pure products.
1
uncorrected. The H and 13C NMR spectra were measured
on a Bruker AC-200 instrument using CDCl3 as solvent.
General Procedure for Synthesis of Substituted 2-
Phenylchroman-4-ones (2a–k)
A mixture of 2-hydroxychalcone (1a–k) (1 mmol) and HM
catalyst (50 mol%) was finely powdered by grinding with
a pestle and mortar for a few minutes and transferred into
a 25-mL round-bottom flask, followed by the addition of
solvent (water, 3 mL) and the mixture was refluxed for 3–
5 h. After completion of the reaction (as monitored by
TLC), the reaction mixture was centrifuged to separate the
catalyst which was washed several times with ethanol. The
combined organic layers were dried over Na2SO4 and the
solvent was removed under reduced pressure. The products
were purified by recrystallization from CHCl3-petroleum
ether.
Ethyl
4-(3-methoxyphenyl)-2-methyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (7g): off-white solid; mp
197–1998C; 1H NMR (400 MHz, CDCl3, Me4Si): d=9.35
(brs, 1H, NH), 7.33–7.29 (m, 1H), 6.90 (d, J=7.7 Hz, 1H),
6.89–6.85 (m, 2H), 5.10 (s, 1H), 4.20 (q, J=7.3 Hz, 2H),
3.88 (s, 3H, OCH3), 2.73–2.68 (m, 3H), 2.44–2.39 (m, 3H),
2.15–1.93 (m, 3H), 1.35 (t, J=7.3 Hz, 3H); 13C NMR
(100 MHz, CDCl3, Me4Si): d=194.6, 166.9, 158.8, 151.4,
149.2, 144.9, 128.8, 113.6, 110.3, 103.3, 59.0, 54.7, 39.4, 36.7,
35.4, 26.1, 20.8, 18.2, 14.1; ESI-MS: m/z=328.15 (M+H)+;
anal. calcd. for C19H21NO4: C 69.71, H 6.47, N 4.28; found:
C 69.68, H 6.48, N 4.30.
2-Pyridin-3-yl-chroman-4-one (2b): yellow oil; 1H NMR
(400 MHz, CDCl3, Me4Si): d=8.75–8.65 (m, 2H, Ar-H),
7.96–7.93 (m, 1H), 7.84(d, J=7.3 Hz, 1H), 7.56–7.51 (m,
1H), 7.39 (dd, J=8 Hz, J=4.4 Hz, 1H), 7.10–7.0 (m, 2H),
5.55 (dd, J=13.2 Hz, J=2.9 Hz, 1H, OCH), 3.09 (dd, J=
16.8 Hz, J=13.2 Hz, 1H, -CHCO), 2.93 (dd, J=16.8 Hz, J=
2.9 Hz, 1H, CHCO); 13C NMR (100 MHz, CDCl3, Me4Si):
d=190.9 (C=O), 161.0, 150.0, 147.7, 136.2, 134.3, 133.6,
127.0, 123.6, 121.9, 120.8, 117.9, 77.24 (CH), 44.2 (CH2; IR
(KBr): nmax =1695 cmÀ1 (C=O); anal. calcd. for C14H11NO2:
C 74.65, H 4.92, N 6.22; found: C 74.60, H 4.90, N 6.28.
Ethyl
4-(2,4-dichlorophenyl)-2-methyl-5-oxo-1,4,5,6,7,8-
hexahydroquinoline-3-carboxylate (7k): off-white solid; mp
245–2478C; 1H NMR (400 MHz, CDCl3, Me4Si): d=9.42
(brs, 1H, NH), 7.56–7.55 (m, 1H), 7.49–7.48 (m, 2H), 5.38
(s, 1H), 4.15 (q, J=7.3 Hz, 2H), 2.73–2.66 (m, 4H), 2.43–
2.28 (m, 3H), 2.13–2.05 (m, 1H), 1.97–1.88 (m, 1H), 1.30 (t,
J=7.3 Hz, 3H); 13C NMR (100 MHz, CDCl3, Me4Si); d=
194.2, 166.6, 151.8, 145.2, 144.5, 132.7, 130.7, 128.1, 127.0,
110.3, 102.7, 59.0, 36.7, 34.6, 26.1, 20.7, 18.1, 14.1; ESI-MS:
m/z=366.06 (M+H)+, 367.06 (M+2)+; anal. calcd. for
C18H17Cl2NO3: C 59.03, H 4.68, N 3.82; found: C 59.08, H
4.70, N 3.85.
General Procedure for Synthesis of the 3-Hydroxy-2-
phenylchroman-4-one (3)
Supporting Information
SEM and XRD data of recycled catalyst, EDX and TGA
data of fresh hydromagnesite catalyst and the HM catalyst
A mixture of 2-hydroxychalcone (1a) (1 mmol) and HM cat-
alyst (50 mol%) was finely powdered by grinding with
a pestle and mortar for a few minutes and transferred to
a 25-mL round-bottom flask, followed by addition of 30%
hydrogen peroxide (0.6 mL) and water (3 mL), the mixture
was then heated at 808C for 2 h. After completion of the re-
action (as monitored by TLC), the reaction mixture was
centrifuged to separate the catalyst which was washed sever-
al times with ethanol. The combined organic layers were
dried over Na2SO4 and the solvent was removed under re-
duced pressure. The recrystallization of crude product from
methanol gave the pure product 3.
3-Hydroxy-2-phenylchroman-4-one (3): colourless nee-
dles; mp 178–1808C; 1H NMR (400 MHz, CDCl3, Me4Si):
d=7.95 (d, J=8 Hz, 1H, Ar-H), 7.61–7.44 (m, 6H), 7.12 (t,
J=8 Hz, 1H), 7.06 (d, J=8 Hz, 1H), 5.15 (d, J=12.4 Hz,
1H), 4.65(d, J=12.4 Hz, 1H); 13C NMR (100 MHz, CDCl3,
Me4Si): d=194.2 (C=O), 161.7, 136.9, 136.2, 129.3, 128.6,
127.5, 127.3, 122, 118.4, 118.1, 83.8 (CH), 73.6 (CH2); IR
1
loading study as well as H and 13C NMR spectra of flavan-
AHCTUNGTREGoNNNU ne 2b, flavonol 3 and 1,4-dihydropyridines (7g, 7k) are
available in the Supporting Information.
Acknowledgements
DSR thanks Department of Science and Technology New
Delhi, India (SR/S1/OC-08/2008), and University of Delhi,
Delhi, India for financial support. UCR is thankful to UGC
and SM is thankful to CSIR for the award of junior and
senior research fellowships, respectively. Thanks to USIC-
CIF, University of Delhi, for analytical data. We are thankful
to Dr. I. Mukhopadhyay for his suggestions in preparing the
hydromagnesite material.
Adv. Synth. Catal. 2013, 355, 3170 – 3178
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3177

U. Chinna Rajesh et al.
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Adv. Synth. Catal. 2013, 355, 3170 – 3178