Evaluation of silica-H2SO4 as an efficient heterogeneous catalyst for the synthesis of chalcones

Article abstract of DOI:10.3390/molecules180810081

We report an efficient silica-H₂SO₄ mediated synthesis of a variety of chalcones that afforded the targeted compounds in very good yield compared to base catalyzed solvent free conditions as well as acid or base catalyzed refluxing conditions.

Full text of DOI:10.3390/molecules180810081

Molecules 2013, 18, 10081-10094; doi:10.3390/molecules180810081
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Evaluation of Silica-H2SO4 as an Efficient Heterogeneous
Catalyst for the Synthesis of Chalcones
Aeysha Sultan 1, Abdul Rauf Raza 1,*, Muhammad Abbas 1, Khalid Mohammed Khan 2,
Muhammad Nawaz Tahir 3 and Nazamid Saari 4,*
1
Ibn e Sina Block, Department of Chemistry, University of Sargodha, Sargodha 40100, Pakistan;
E-Mails: blackhawk.aries@gmail.com (A.S.); abbas12396@yahoo.com (M.A.)
2
HEJ Research Institute of Chemistry, International Centre for Chemical & Biological Sciences,
University of Karachi, Karachi 75270, Pakistan; E-Mail: khalid.khan@iccs.edu
3
Ibn ul Haithum Block, Department of Physics, University of Sargodha, Sargodha 40100, Pakistan;
E-Mail: dmntahir_uos@yahoo.com
4
Department of Food Science, University Putra Malaysia, UPM 43400, Serdang, Malaysia;
E-Mail: nazamid@upm.edu.my
* Authors to whom correspondence should be addressed; E-Mails: roofichemist2012@gmail.com
(A.R.R.); nazamid@upm.edu.my (N.S.); Tel.: +92-48-600-7432 (A.R.R.); +603-8946-8385 (N.S.);
Fax: +92-48-923-0799 (A.R.R.); +603-8942-3552 (N.S.).
Received: 19 July 2013; in revised form: 5 August 2013 / Accepted: 7 August 2013 /
Published: 20 August 2013
Abstract: We report an efficient silica-H2SO4 mediated synthesis of a variety of chalcones
that afforded the targeted compounds in very good yield compared to base catalyzed
solvent free conditions as well as acid or base catalyzed refluxing conditions.
Keywords: silica-H2SO4; solvent free conditions; chalcone; arylidene indanone; arylidene
tetralone; Claisen-Schmidt condensation
1. Introduction
The generic term chalcones refer to compounds with a main 1,3-diphenylprop-2-enone core.
Chemically chalcones are open chain flavonoids with two aromatic rings linked via a three carbon
α,β-unsaturated enone system. These compounds are widely found in numerous species of plant, which
are used as traditional folk medicines for treatment of a large number of diseases. Whether synthetic or

Molecules 2013, 18
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isolated from plants, chalcones have been found to be associated with diverse biological applications
such as antiinflammatory [1], antipyretic, antimutagenic [2], antioxidant [3], cytotoxic, antitumor [4]
and a large list yet to be mentioned.
Owing to their diverse biological activities, many synthetic strategies toward these compounds have
been developed that involve Claisen-Schmidt condensations of substituted acetophenones with
aldehydes. Different reagents employed for the chalcone synthesis include aq. alcoholic alkali [5], dry
HCl [6], anhydrous AlCl3 [7], POCl3 [8], aqueous Na2B4O7·10H2O [9], HClO4 [10], BF3 [11],
Mg(OtBu)2 [12], graphite oxide [13,14] hydroxyapetite [15,16], phosphate derivatives [17], organo Cd
compounds, SnCl4 and the use of animal bone meal (ABM) as a heterogeneous catalyst [18]. In
addition to these Gupta and Boss et al., in their separate studies synthesized chalcones under microwave
irradiation in the presence of NaOH [19,20]. Seedhar et al., carried out chalcone synthesis in
polyethylene glycol (PEG) as an environment friendly solvent [21]. Boukhvalov et al. carried out a
computational investigation of the potential role of graphene oxide as a heterogenous catalyst [22].
With increasing concerns about environmental pollution, synthetic strategies are been developed
that involve the use of less or no solvent. Similarly the heterogeneous catalysis is preferred over
homogenous catalysis because of the work-up, economical and environmental advantages of the
former. Silica-H2SO4 (SSA) is a versatile, selective and a powerful catalyst that has been explored for
various organic transformations, such as the synthesis of heterocyclic compounds [23–27], cross-aldol
condensations [28], Michael additions [29], protection [30,31], deprotection [32] and oxidation
reactions [33]. The major advantages of SSA include: ease of preparation, ease of removal from
reaction mixtures, comparatively mild conditions as compared to H2SO4 as well as NaOH. Since it
requires no use of solvent, therefore it is economical as well as environmentally friendly and most
important thing is that it can be recycled.
In this article, we wish to report an efficient and versatile procedure for the synthesis of chalcones
in the presence of SSA and a comparison of the results of our synthesis to different methods in order to
evaluate the effectiveness of the SSA-mediated synthesis of chalcones.
2. Results and Discussion
For the preparation of chalcones, four different reagents/reaction conditions were chosen: refluxing
conditions using MeOH as a solvent in the presence of stoichiometric amount of H2SO4 or NaOH,
grinding the reactants with NaOH pallets under neat conditions (SF) and by heating the reactants with
SSA in the absence of any solvent.
The SSA was prepared by two different reported methods. One method involves the addition of
H2SO4 to a suspension of silica gel in Et2O, followed by the evaporation of the solvent under reduced
pressure and heating the resulting silica gel at 120 °C for 3 h [34]. The other method involves the
addition of silica gel to HSO3Cl along with subsequent trapping of HCl produced during the reaction [35].
The SSA obtained by both methods was similar in form, i.e., a white solid, and showed similar results.
In order to determine the optimum amount of SSA required for a given transformation, the simplest
chalcone 3a (obtained by condensing PhAc with PhCHO in the presence of varying amounts of SSA from
0.005 to 0.1 g) was synthesized (Scheme 1).

Molecules 2013, 18
10083
Scheme 1. SSA-assisted synthesis of chalcone 3a.
O
O
Ph
PhCHO
+
1a (1 eq)
2 (1.05 eq)
3a
It is observed that best results are obtained with 0.02 g of SSA. If less than 0.02 g of SSA was
employed the yield of the product was low or the transformation was incomplete. An increase in
amount of SSA resulted in a slight increase in yield, but decomposition of the product and difficult
isolation of the product was observed upon increasing (≥0.05 g) the amount of SSA (Table 1).
Table 1. Determination of optimum amount of SSA for the preparation of chalcone 3a.
Entry
SSA (g)
0.005
0.01
0.01
0.02
0.02
0.02
0.05
0.1
Solvent
Time (Temperature, °C )
4 h (reflux)
6 h (reflux)
2 h (65)
%Yield ¥
1
2
3
4
5
6
7
8
MeOH
*
*
CH2Cl2
-
-
-
-
-
-
28
-
8 h (rt)
1 h (65)
91
#
0.5 h (100)
0.5 h (65)
94
^
0.5 h (65)
#
* A number of spots were observed on TLC along with reactants; the SSA became a black powder and
reaction workup afforded a number of spots on TLC; ^ no product could be isolated and TLC of the reaction
mixture indicated the formation of a number of compounds; ¥ All yields reported above are isolated yields.
In order to confirm the effectiveness of SSA three control experiments were performed, which
include heating reactants with silica gel under solvent free conditions, using H2SO4 (without silica gel)
in MeOH (at 65 °C ) and by heating the aldehyde and ketone in the presence of silica gel and H2SO4 at
65 °C both in the presence and absence of methanol (used as a solvent). No product formation was
observed when only silica gel was used. When the reactants were heated together with silica and
H2SO4 in the absence of solvent, blackening of the contents of reaction flask was observed with no
transformation occurred, even after 4 h. Heating the reactants with silica and H2SO4 in MeOH yielded
1,3-diphenylprop-2-enone (3a) in less than 10% yield after 5 h. Heating the reactants in H2SO4 using
MeOH at 65 °C afforded the chalcone 3a in 28% yield after 4 h; however, refluxing the methanolic
solution of reactants with H2SO4 afforded chalcone 3a in 38% after 4 h.
The catalyst is not only removed easily, but can be recycled. The catalyst was recovered by simple
filtration after the addition of CH2Cl2 followed by partitioning between H2O and the organic layer. The
residual catalyst was washed with acetone in order to extract any remaining product adsorbed on the
catalyst surface, and it was then reactivated by placing in an oven for 30 min at 100 °C . The recovered
catalyst was used three times for the synthesis of 1,3-diphenylprop-2-enone and almost the same yield
was obtained as observed in the first run.

Molecules 2013, 18
10084
2.1. Synthesis of Open Chain Chalcones 3a–o
When substituted PhAc 1 and ArCHO 2 were condensed in the presence of different reagents, the
capricious yield of the products 3 depends upon the nature of reagent used. In general, the
base- catalyzed reaction under refluxing conditions gave the lowest yields in almost all cases. The
effect was more pronounced when either substrate (i.e., 1 or 2) contains –I and +R groups (such as OH,
NMe2) or –I and –R groups (such as NO2). The acid catalyzed reaction also suffered the problem of
low yields. The low yield with base-catalyzed refluxing conditions was attributed to the oxidation of
aldehydes to their corresponding carboxylic acids via the Cannizarro reaction, which results in an
overall decrease in the active concentration of aldehyde 2. The oxidation of aldehydes to carboxylic
acids was much pronounced with para-substituted 2. The solvent free (SF) conditions led to quite a
high yield of the product; however, the yields were quite low when either or both of the reactants
contains –I and +R/–R groups. The yields of such substrates under SSA conditions are quite higher
1
(Scheme 2. Table 2). The formation of the chalcones 3a–o was confirmed by H-NMR that indicated
the presence of Jtrans (14.9–17.4 Hz). The mass spectra were also in agreement with the formation of
the targeted chalcones.
Scheme 2. Synthesis of chalcones 3 under different reaction conditions.
O
O
3
Ar
2
ArCHO
+
R
R
1 (1 eq)
2 (1.05 eq)
3
Table 2. Comparison of yield using different reagents and δ of olefinic protons in 3a–o.
%Yield
NaOH # SF^ SSA ¥
1H-δ ! (J §)
Entry
R
Ar
3
*
H2SO4
54
H2
H3
a
b
c
H
Ph
Ph
3a
3b
3c
3d
3e
3f
45
51
43
24
41
32
73
79
13
-
77
82
71
73
85
89
92
86
29
35
40
25
33
83
76
91
95
83
88
88
92
89
94
80
83
87
76
74
96
92
7.60 (16.4)
7.58 (15.9)
7.35 (16.8)
7.43 (15.6)
7.54 (17.1)
7.43 (15.4)
7.56 (17.4)
7.55 (15.6)
6.86 (14.9)
7.62 (16.0)
7.50 (16.8)
7.54 (15.8)
7.38 (16.0)
7.61 (16.6)
7.63 (16.1)
8.12 (16.4)
7.98 (15.9)
7.59 (16.8)
7.81 (15.6)
7.83 (17.4)
7.79 (15.4)
7.88 (17.4)
7.88 (15.6)
7.58 (14.9)
8.02 (16.0)
7.77 (16.8)
7.83 (15.8)
7.79 (16.0)
8.18 (16.5)
8.03 (16.1)
3′-OH
3′-OH
4′-OH
4′-OH
4′-OH
4′-Me
4′-Me
4′-Me
3′-NO2
3′-NO2
3′-NO2
3′-NO2
4′-Cl
25
2-furyl
Ph
38
d
e
48
2-furyl
4-MeOPh
Ph
45
f
58
g
h
i
3g
3h
3i
62
2-furyl
4-Me2NPh
Ph
54
<10
<10
15
j
3j
k
l
2-furyl
4-Me2NPh
4-MeOPh
Ph
3k
3l
-
23
-
m
n
o
3m
3n
3o
19
-
78
68
64
4′-Cl
2- MeOPh
75
#
^
* 1.5 equivalent to 1, 5 h reflux in MeOH; 1.15 equivalents to 1, 3 h reflux; SF (NaOH mediated solvent
¥
free) 3 equivalents of NaOH to 1, grinding in neat conditions; SSA heating at 65 °C for 1.5 h under neat
!
§
conditions; chemical shifts are reported in ppm; coupling constants are reported in Hz (both protons
showed doublets in all cases).

Molecules 2013, 18
10085
2.2. Synthesis of Tetralone- and Indanone-Based Chalcones 5a–m
After the successful synthesis of various substituted chalcones 3a–o, the effect of reagent on the
yield of tetralone- and indanone-based chalcones was studied. For this purpose the tetralone and/or
indanone was allowed to condense with various aldehydes in the presence of acid, base, solvent free
conditions and SSA. The trends were almost similar as observed in case of 3a–o. In most cases a
molecular ion 6a or 6b was observed as a stable radical cation (Scheme 3, Table 3).
Scheme 3. Synthesis of arylidene tetralone and arylidene indanones 5 under different conditions.
O
O
O
O
1'
C
C
Ar
Ar
Ar
70 eV
ArCHO
+
n
n
n
n
4 (1 eq)
5
6a
6b
2 (1.05 eq)
Table 3. Comparison of yield using different reagents, δ of H1′ and m/z of [M]+· in 5a–m.
1H-δ !
(H1′)
7.93
7.44
6.97
8.13
7.64
8.53
7.18
6.98
7.56
7.82
6.69
8.27
6.81
[6a]+ or [6b]+
(% abundance)
220 (64)
%Yield
H2SO4 * NaOH#
Entry
n
Ar
5
SF^
83
78
85
82
79
53
80
76
85
62
85
71
79
SSA ¥
87
91
82
97
90
72
86
80
87
94
89
85
87
a
b
c
d
e
f
0
0
0
0
0
0
0
1
1
1
1
1
1
Ph
2-furyl
5a
5b
5c
5d
5e
5f
35
48
12
73
75
13
75
66
72
21
76
20
78
41
52
-
210 (100)
263 (100)
250 (76)
4-Me2NPh
4-MeOPh
3-MeOPh
3-NO2Ph
3,4-(OMe)2Ph
Ph
35
56
<10
63
54
68
17
71
19
42
250 (100)
265 (42)
g
h
i
5g
5h
5i
280 (100)
234 (56)
2-furyl
224 (100)
277 (52)
j
4-Me2NPh
4-MeOPh
3-NO2Ph
3-ClPh
5j
k
l
5k
5l
264 (100)
279 (29)
m
5m
268, 270 (38, 12)
^
* 1.5 equivalent to 1, 5 h reflux in MeOH; # 1.01 equivalents to 1, 3 h reflux; SF (NaOH mediated solvent
¥
free) 3 equivalents of NaOH to 1, grinding under neat conditions; SSA (0.02 g), heating at 65 °C for 1.5 h
under neat condition; !chemical shifts are reported in ppm.
The change in ring size of tetralone and indanone didn’t affect the yield of the product(s). The
1
formation of arylidene indanone/tetralones was confirmed by H-NMR that indicated the presence of
an olefinic proton that appeared as a singlet (6.69–7.82 ppm) in most of the cases depending upon the
–I and –R/+R effect of the locants at 2 (Figure 3). The XRD of a couple of products (5g and 5i, one
from each case) confirmed the formation of a new C=C bond (1.337Å between C1 & C10 and 1.340Å
between C10 & C11 respectively) (Figure 1) [36].

Molecules 2013, 18
10086
Figure 1. The ORTEP diagram of (a) 5g. (b) 5i.
An aldol product 7b was isolated as a major product in case of H2SO4-mediated condensation
of 4 with 2-Cl-5-NO2PhCHO; whereas the base or SSA catalyzed reactions afforded the desired enone 7a.
Due to steric factors no o-substituted substrate was used in any previous case. The H-bonding, forming
a six member ring, between Cl or carbonyl O and alcoholic H would probably be the reason of the
failure of the dehydration in 7b (Figure 2a). The XRD of 7b showed a new C-O (1.418Å) and O-H
(0.821Å) bond formation instead of C=C (Figure 2b) [37].
Figure 2. (a) Formation of 7a and 7b under different reaction conditions: i) NaOH reflux
(7a, 43%), SF (7a, 71%); SSA (7a, 82%); ii) H2SO4 reflux (7b, 73%). (b) The ORTEP
diagram of 7b.
3. Experimental
The TLC was carried out on pre-coated silica gel (0.25 mm thick layer over Al sheet, Merck,
Darmstadt, Germany) with fluorescent indicator. The spots were visualized under UV lamps (λ 365
and 254 nm) of 8 W power or KMnO4 dip and heating. The compounds were purified either on a glass
column packed silica gel (0.6–0.2 mm, 60Å mesh size, Merck) or by crystallization. All solutions were
concentrated under reduced pressure (25 mm of Hg) on a rotary evaporator (Laborota 4001, Heidolph,
Germany) at 35–40 °C . Melting points were determined using a MF-8 (Gallenkamp, Burladingen,
Germany) instrument and are reported uncorrected. The IR-spectra are recorded on Prestige 21
spectrophotometer (Shimadzu, Japan) as KBr discs. The LREIMS are carried out on a Fisons Autospec
Mass Spectrometer (VG, New Jersey, USA). The 1H (300, 400 and 500 MHz) and 13C-NMR (75 MHz)
are recorded on AM-300, 400 and 500 MHz instruments (Bruker, Massachusetts, USA) in CDCl3
using TMS as internal standard.

Molecules 2013, 18
10087
3.1. Preparation of SSA
Method A: The H2SO4 was added to a stirred suspension of silica gel in Et2O. After stirring for 1 h, the
solvent was evaporated under reduced pressure. The resulting SSA was placed in an oven at 120 °C for
3 h, which afforded SSA as a white solid.
Method B: The silica gel was added to HSO3Cl along with subsequent trapping of HCl produced
during the reaction. The suspension thus formed was stirred at room temperature for 3 h and the
resultant product was dried in fume-hood to remove any trapped HCl produced during the reaction.
The SSA obtained in this manner was white sand like solid.
3.2. Representative Procedure for H2SO4 Catalyzed Synthesis of Chalcones under Reflux
The PhAc (1 mL, 0.90 g, 7.53 mmol, 1 eq.) and PhCHO (0.84 g, 7.91 mmol, 1.05 eq.) were added
to a stirred solution of H2SO4 (0.5 mL, 0.86 g, 8.66 mmol, 1.15 eq.) in MeOH (15 mL) and the
resulting reaction mixture was refluxed for 3 h. After the completion of reaction, the solvent was
evaporated under a stream of N2. The resulting reaction mixture was neutralized with 10% aq.
NaHCO3 and partitioned between H2O (50 mL) and EtOAc (3 × 25 mL). The combined organic
extract was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford
product as white amorphous solid. Crystallization from CH2Cl2 afforded product as colorless needles
(0.89 g, 54%).
3.3. Representative Procedure for NaOH Catalyzed Synthesis of Chalcones under Reflux
The PhAc (1 mL, 0.90 g, 7.53 mmol, 1 eq.) and PhCHO (0.84 g, 7.91 mmol, 1.05 eq.) were added
to a stirred solution of NaOH (0.35 g, 8.66 mmol, 1.15 eq.) in MeOH (15 mL) and the resulting
reaction mixture was refluxed for 3 h. After the completion of reaction, the solvent was evaporated
under a stream of N2. The resulting reaction mixture was acidified with dil. aq. HCl and partitioned
between H2O (50 mL) and EtOAc (3 × 25 mL). The combined organic extract was dried over
anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford product as white
amorphous solid. Crystallization from CH2Cl2 afforded product as colorless needles (0.74 g, 45%).
3.4. Representative Procedure for NaOH Catalyzed Synthesis of Chalcones under Solvent
Free Conditions
The PhAc (1 mL, 0.90 g, 7.53 mmol, 1 eq) and PhCHO (0.84 g, 7.91 mmol, 1.05 eq) were ground
together in a mortar and pestle in the presence of NaOH (0.30 g, 7.60 mmol, 1.01 eq) for 30 min. The
reaction mixture was neutralized and extracted with Et2O (3 × 25 mL). The combined organic extract
was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the
enone as colourless solid (1.27 g, 77%).
3.5. Representative Procedure for the SSA Catalysed Synthesis of Chalcones
The SSA (0.02 g) was added to a well stirred suspension of PhAc (1 mL, 0.90 g, 7.53 mmol, 1 eq.)
and PhCHO (0.84 g, 7.91 mmol, 1.05 eq.) and the resulting mixture was heated at 65 °C for 1.5 h. The

Molecules 2013, 18
10088
reaction mixture was cooled to room temperature and partitioned between brine (25 mL) and CH2Cl2
(3 × 15 mL) and solid SSA was filtered off. The SSA was washed with acetone (25 mL) to ensure
desorption of product on SSA surface. The combined organic extract was washed with brine (3 × 25 mL)
and the organic extract was dried over anhydrous Na2SO4, filtered and concentrated under reduced
pressure to afford the chalcone as colorless solid (1.48 g, 91%).
1,3-Diphenylprop-2-enone (3a): Rf: 0.58 (EtOAc/n-hexane, 1:3); M.p.: 57 °C (Lit. 56–57 °C )[38]; IR
(KBr): ύmax (cm–1) 2930 (=C-H), 1679 (C=O); 1H-NMR (400 MHz, CHCl3, δ in ppm): 7.18–7.32 (5H, m,
H2′-H4′), 7.46-7.55 (3H, m, H3′′, H4′′), 7.60 (1H, d, J = 16.4 Hz, H2), 7.89 (2H, d, J = 7.8 Hz, H2′′), 8.12
13
(1H, d, J = 16.4 Hz, H3); C-NMR (75 MHz, CDCl3, δ in ppm): 123.3 (d, C2), 125.4, 126.9, 128.4,
129.2 (2 ×, d, C2′, C3′, C2′′, C3′′), 127.1, 133.8 (d, C4′, C4′′), 134.2, 135.5 (s, C1′, C1′′), 144.1 (d, C3),
187.5 (s, C1); EI-MS (m/z, amu): 208 [M]+ (54%), 131 [M − Ph]+ (100%), 105 [PhCO]+ (98%).
3-(4′-Hydroxyphenyl)-1-phenylpropenone (3d): Rf: 0.48 (EtOAc/ n-hexane, 3:1); M.p.: 44 °C
1
(Lit. 35–45 °C )[38]; IR (KBr): ύmax (cm–1) 3320 (O-H, bs), 2885 (=C-H), 1669 (C=O); H-NMR (400
MHz, CHCl3, δ in ppm): 6.87 (2H, d, J = 7.6 Hz, H3′), 7.14–7.28 (5H, m, Ph-H), 7.43 (1H, d, J = 15.6 Hz,
13
H2), 7.65 (2H, d, J = 7.5 Hz, H2′), 7.81 (1H, d, J = 15.6 Hz, H3), 10.10 (1H, bs, OH); C-NMR (75
MHz, CDCl3, δ in ppm): 112.8 (2×, d, C3′), 121.0 (d, C2), 126.2, 128.1, 129.9 (2 ×, d, C2′, C2′′, C3′′), 129.4
(s, C1′′), 128.3 (d, C4′′), 132.8 (s, C1′), 140.8 (d, C3), 158.3 (s, C4′), 187.6 (s, C1); EI-MS (m/z, amu): 224
[M]+ (54%), 131 [PhCH=CHCO]+ (100%, A), 121 [M − A]+ (94%).
3-(Furan-2′′-yl)-1-p-tolylpropenone (3h): Rf: 0.53 (EtOAc/ n-hexane, 1:3); M.p.: 64–67 °C (Lit.
1
62–64 °C )[39]; IR (KBr): ύmax (cm–1) 2898 (=C-H), 1672 (C=O); H-NMR (400 MHz, CHCl3,
δ in ppm): 2.27 (3H, s, Me), 6.57 (1H, dd, J = 3.2, 1.8 Hz, H4′′), 6.78 (1H, d, J = 3.2 Hz, H3′′), 7.22
(2H, d, J = 7.5 Hz, H3′), 7.55 (1H, d, J = 15.6 Hz, H2), 7.67 (2H, d, J = 7.5 Hz, H2′), 7.82 (1H, d,
J = 1.8 Hz, H5′′), 7.88 (1H, d, J = 15.6 Hz, H3); 13C-NMR (75 MHz, CDCl3, δ in ppm): 19.6 (q, CH3),
110.4, 111.9, 128.3, 129.2, 129.4, 129.6, 129.9 (d, C2, C2′, C3′, C5′, C6′, C3′′, C4′′), 134.1 (s, C1′/C4′),
141.8 (d, C3′/C5′′), 142.9 (s, C1′/C4′), 143.5 (d, C3′/C5′), 154.8 (s, C1′′), 189.3 (s, C1); EI-MS (m/z, amu):
212 [M]+ (79%), 121 [M − C6H4Me]+ (94%), 119 [MeC6H4CO]+ (100%).
3-(4′′-Dimethylaminophenyl)-1-(3′-nitrophenyl)propenone (3l): Rf: 0.46 (EtOAc/ n-hexane, 1:1);
M.p.: 107–111 °C (Lit. 110 °C )[40]; IR (KBr): ύmax (cm–1) 2999 (=C-H), 1663 (C=O), 1545 (N=O);
1H-NMR (400 MHz, CHCl3, δ in ppm): 2.94 (6H, s, N(CH3)2), 6.54 (2H, d, J = 7.8 Hz, H3′′), 7.18 (2H, d,
J = 7.8 Hz, H2′′), 7.54 (1H, d, J = 15.8 Hz, H2), 7.68 (1H, t, J = 6.8 Hz, H5c), 7.83 (1H, d, J = 15.8 Hz,
H3), 7.96 (1H, dd, J = 6.8, 2.4 Hz, H6′), 8.31 (1H, d, J = 6.8 Hz, H4′), 8.66 (1H, t, J = 2.4 Hz, H2′);
13C-NMR (75 MHz, CDCl3, δ in ppm): 42.7, 42.9 (q, N-CH3), 112.9 (2×, d, C3′′), 120.2 (d, C2), 122.4
(s, C1′′), 126.7 (2×, d, C2′′), 129.8, 130.4, 130.8, 133.6 (d, C2′, C4′-C6′), 135.1 (s, C1′), 140.2 (s, C4′′),
144.4 (d, C3), 149.0 (s, C3′), 188.2 (s, C1); EI-MS (m/z, amu): 296 [M]+ (18%), 174 [M − C6H4NO2]+
(100%, A), 150 [NO2C6H4CO]+ (23%), 146 [A − CO]+ (100%).
1-(4′-Chlorophenyl)-3-(4′′-methoxyphenyl)propenone (3o): Rf: 0.57 (EtOAc/n-hexane, 1:1);
M.p.: 67–68 °C (Lit. 68–70 °C )[41]; IR (KBr): ύmax (cm–1) 3007 (=C-H), 1658 (C=O), 766 (C-Cl);
1H-NMR (400 MHz, CHCl3, δ in ppm): 3.73 (3H, s, OMe), 6.65 (2H, d, J = 7.8 Hz, H3′′), 6.98 (2H, d,

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J = 7.8 Hz, H3′), 7.41 (2H, d, J = 7.5 Hz, H2′′), 7.63 (1H, d, J = 16.1 Hz, H2), 7.67 (2H, d, J = 7.5 Hz, H2′),
8.03 (1H, d, J = 16.1 Hz, H3); 13C-NMR (75 MHz, CDCl3, δ in ppm): 63.2 (q, OCH3), 114.3 (2×, d, C3′′),
119.0 (s, C2), 127.3 (2×, d, C2′), 128.8 (2×, d, C2′′), 129.7 (2×, d, C3′), 130.2 (s, C1′′), 136.7 (s, C4′),
138.8 (s, C1′), 145.1 (d, C3), 161.0 (s, C4′′), 189.9 (s, C1); EI-MS (m/z, amu): 272, 274 [M]+ (56, 17%),
161 [M − C6H4Cl]+ (100%).
2-(Furan-2′′-yl)methyleneindan-1-one (5b): Rf: 0.55 (EtOAc/ n-hexane, 1:3); M.p.: 116 °C
(Lit. 118–119 °C )[42]; IR (KBr): ύmax (cm–1) 2991 (=C-H), 1616 (C=O); 1H-NMR (CDCl3, 400 MHz,
δ in ppm): 4.04 (2H, s, H3), 6.53–6.54 (1H, m, H4′′), 6.75 (1H, d, J = 3.2 Hz, H3′′), 7.41 (1H, t, J = 7.2 Hz,
H6), 7.44 (1H, s, H1′), 7.53 (1H, d, J = 7.2, H4), 7.57-7.61 (2H, m, H5, H5′′), 7.87 (1H, d, J = 7.2 Hz,
H7); 13C-NMR (75 MHz, CDCl3, δ in ppm): 20.9 (t, C3), 110.4, 112.3 (d, C3′′, C4′′), 125.1, 127.8, 128.2,
129.9 (d, C4-C7), 136.1 (d, C1′), 136.9, 137.5, 138.3 (s, C2, C3a, C7a), 142.8 (d, C5′′), 154.1 (s, C2′′),
188.7 (s, C1); EI-MS (m/z, amu): 210 [M]+ (100%), 182 [M − CO]+ (18%, A), 181 [A − H]+ (84%).
2-(4′′-Dimethylaminobenzylidene)indan-1-one (5c): Bright yellow solid; Rf: 0.52 (EtOAc/n-hexane,
1
1:1); M.p.: 167 °C (Lit. 168 °C )[43]; IR (KBr): ύmax (cm–1) 2933 (=C-H), 1656 (C=O); H-NMR
(CDCl3, 400 MHz, δ in ppm): 3.07 (6H, s, NMe2), 4.00 (2H, s, H3), 6.97 (1H, s, H1′), 7.41 (1H, d,
J = 6.4 Hz, H4), 7.54–7.63 (6H, m, H5, H6, H2′′, H3′′), 7.88 (1H, d, J = 6.8 Hz, H7); 13C-NMR (75 MHz,
CDCl3, δ in ppm): 24.5 (t, C3), 43.2, 43.4 (q, N-CH3), 112.8 (2×, d, C3′′), 123.8 (s, C1′′), 125.2 (2×, d,
C2′′), 126.7, 128.5, 129.4, 130.2 (d, C4-C7), 133.9 (d, C1′), 134.0, 137.2, 137.8 (s, C2, C3a, C7a), 143.5 (d,
C4′′), 186.9 (s, C1); EI-MS (m/z, amu): 263 [M]+ (100%), 235 [M − CO]+ (43%, A), 234 [A − H]+ (71%).
2-(3′′-Methoxybenzylidene)indan-1-one (5e): Colorless solid; Rf: 0.58 (EtOAc/ n-hexane, 1:3);
1
M.p.: 135 °C (Lit. 138 °C )[44]; IR (KBr): ύmax (cm–1) 2948 (=C-H), 1679 (C=O); H-NMR (CDCl3,
300 MHz, δ in ppm): 3.86 (3H, s, OCH3), 4.04 (2H, s, H3), 6.94 (1H, dd, J = 8.1, 1.8 Hz, H6′′),
7.18 (1H, bs, H2′′), 7.26 (1H, d, J = 8.0 Hz, H4′′), 7.37 (1H, t, J = 7.8 Hz, H6), 7.41 (1H, t, J = 7.2 Hz,
H5′′), 7.54 (1H, d, J = 7.2 Hz, H4), 7.58–7.63 (2H, m, H5, H1′), 7.90 (1H, d, J = 7.5 Hz, H7); 13C-NMR
(75 MHz, CDCl3, δ in ppm): 25.2 (t, C3), 56.8 (q, O-CH3), 110.5, 112.4, 117.5 (d, C2′′,C4′′, C6′′), 125.8,
126.5, 127.5, 128.9, 130.0 (d, C4-C7, C5′′), 135.4 (d, C1′), 135.8, 136.2, 137.9, 138.5 (s, C2, C3a, C7a, C1′′),
159.9 (s, C3′′), 187.9 (s, C1); EI-MS (m/z, amu): 250 [M]+ (100%), 249 [M − H]+ (56%).
2-(3′′-Nitrobenzylidene)indan-1-one (5f): Pale yellow solid; Rf: 0.54 (EtOAc/ n-hexane, 3:1);
1
M.p.: 119–121 °C ; IR (KBr): ύmax (cm–1) 2987 (=C-H), 1679 (C=O), 1565 (N=O); H-NMR (CDCl3,
500 MHz, δ in ppm): 4.11 (2H, s, H3), 7.45 (1H, t, J = 7.5 Hz, H6), 7.60 (1H, d, J = 7.5 Hz, H4), 7.64
(2H, t, J = 8.0 Hz, H5, H5′′), 7.68 (1H, dd, J = 2.0, 2.0 Hz, H2′′), 7.92 (1H, d, J = 7.5 Hz, H4′′), 7.93 (1H,
13
d, J = 7.5 Hz, H6′′/H7), 8.24 (1H, dd, J = 8.0, 1.5 Hz, H6′′/H7), 8.53 (1H, s, H1′); C-NMR (75 MHz,
CDCl3, δ in ppm): 24.8 (t, C3), 122.2, 124.0, 125.8, 126.5, 127.5, 128.9, 129.7, 130.0 (d, C4–C7, C2′′,
C4′′–C5′′), 135.9 (d, C1′), 136.0, 136.2, 136.5, 137.4 (s, C2, C3a, C7a, C1′′), 147.7 (s, C3′′), 188.6 (s, C1);
EI-MS (m/z, amu): 265 [M]+ (42%), 219 [M − NO2]+ (35%, A), 218 [A − H]+ (53%).
2-(3′′,4′′-Dimethoxybenzylidene)indan-1-one (5g): off-white solid; Rf: 0.58 (EtOAc/n-hexane, 1:3);
1
M.p.: 182 °C (Lit. 183-185 °C )[45]; IR (KBr): ύmax (cm–1) 3018 (=C-H), 1652 (C=O); H-NMR
(CDCl3, 400 MHz, δ in ppm): 3.93 (3H, s, OMe), 3.95 (3H, s, OMe), 4.02 (2H, s, H3), 6.95 (1H, d,

Molecules 2013, 18
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J = 8.4 Hz, H6′′), 7.18 (1H, s, H1′), 7.30 (1H, d, J = 7.2 Hz, H5′′), 7.42 (1H, t, J = 7.2 Hz, H6), 7.54–7.62
(3H, m, H4, H5, H2′′), 7.90 (1H, d, J = 8.0 Hz, H7); 13C-NMR (75 MHz, CDCl3, δ in ppm): 23.8 (t, C3),
58.9, 61.4 (q, OCH3), 111.6, 113.3, 118.4 (d, C2′′, C5′′, C6′′), 125.8 (s, C1′′), 127.1, 128.9, 129.3, 132.3,
134.9 (d, C4-C8, C1′), 132.4, 136.6, 137.2 (s, C2, C3a, C7a), 146.8, 147.1 (s, C3′′, C4′′), 187.1 (s, C1);
EI-MS (m/z, amu): 280 [M]+ (100%), 279 [M − H]+ (38%), 249 [M − OMe]+ (41%).
2-Benzylidene-3,4-dihydro-2H-naphthalen-1-one (5h): Pale yellow solid; Rf: 0.64 (EtOAc/n-hexane,
1
1:3); M.p.: 96 °C (Lit. 96 °C )[46]; IR (KBr): ύmax (cm–1) 3016 (=C-H), 1656 (C=O); H-NMR (500
MHz, CDCl3, δ in ppm): 2.99 (1H, t, J = 7.2 Hz, H3), 3.13 (2H, t, J = 7.2, H4), 6.98 (1H, bs, H1′),
13
7.21–7.66 (8H, m, H5-H7, H2′′-H4′′), 7.85 (1H, d, J = 7.6 Hz, H8); C-NMR (75 MHz, CDCl3, δ in
ppm): 27.2, 28.9 (t, C3, C4), 127.1, 128.3 (2×, d, C2′′, C3′′), 128.5, 128.6, 129.5 (d, C5, C7, C4′′), 131.8,
132.5, 136.0 (d, C6, C8, C1′), 136.7 (3×, s, C8a, C2, C1′′), 144.2 (s, C4a), 188.6 (s, C1); EI-MS (m/z, amu):
234 [M]+ (56%), 206 [M − CO]+ (23%).
2-(Furan-2′′-yl)methylene-3,4-dihydro-2H-naphthalen-1-one (5i): Colourless solid; Rf: 0.54 (EtOAc/
n-hexane, 1:3); M.p.: 129–131 °C ; IR (KBr): ύmax (cm–1) 2965 (=C-H), 1621 (C=O); 1H-NMR (CDCl3,
300 MHz, δ in ppm): 3.01 (2H, t, J = 6.6 Hz, H4), 3.33 (2H, ddd, J = 5.1, 5.1, 1.8 Hz, H3), 6.53 (1H,
dd, J = 3.3, 1.8 Hz, H4′′), 6.71 (1H, d, J = 3.3 Hz, H3′′), 7.27 (1H, d, J = 7.5 Hz, H5), 7.38 (1H, t, J = 7.5 Hz,
H7), 7.48 (1H, ddd, J = 7.5, 7.5, 1.5 Hz, H6), 7.56 (1H, s, H1′), 7.60 (1H, d, J = 1.5 Hz, H5′′), 8.11 (1H, dd,
J = 7.5, 1.2 Hz, H8); 13C-NMR (75 MHz, CDCl3, δ in ppm): 26.7, 28.4 (t, C3, C4), 112.2 (d, C4′′), 116.6
(s, C3′′), 122.8, 127.0 (d, C5, C7), 128.1 (2×, d, C6, C8), 131.9 (s, C4a/C8a), 133.1 (d, C1′), 133.6 (s, C4a/C8a),
143.5 (s, C2), 144.4 (d, C5′′), 152.5 (s, C2′′), 187.4 (s, C1); EI-MS (m/z, amu): 224 [M]+ (100%), 223
[M − H]+ (42%), 196 [M − CO]+ (26%).
2-(4′′-Dimethylaminobenzylidene)-3,4-dihydro-2H-naphthalen-1-one (5j): Bright yellow solid; Rf: 0.54
(EtOAc/n-hexane, 1:3); M.p.: 35 °C (Lit. 35 °C )[46]; IR (KBr): ύmax (cm–1) 2889 (=C-H), 1665 (C=O);
1H-NMR (CDCl3, 400 MHz, δ in ppm): 2.93 (4H, m, H3, H4), 3.11 [6H, s, N(CH3)2], 7.07–7.47 (7H, m,
H5-7, H2′′, H3′′), 7.82 (1H, s, H1′), 8.09 (1H, d, J = 7.2 Hz, H8); 13C-NMR (75 MHz, CDCl3, δ in ppm):
27.8, 28.7 (t, C3, C4), 40.1 [2×, q, N(CH3)2], 111.6 (s, C1′′), 123.6 (2×, d, C3′′), 127.3, (2×, d, C2′′),
126.8, 127.8, 128.0, 131.0, 132.1 (d, C5, C6, C7, C8, C1′), 132.7, 134.5, 142.9 (s, C2, C8a, C4a), 150.6 (s, C4′′),
187.8 (s, C1); EI-MS (m/z, amu): 277 [M]+ (53%), 276 [M − H]+ (33%), 249 [M − CO]+ (8%).
2-(4′′-Methoxybenzylidene)-3,4-dihydro-2H-naphthalen-1-one (5k): Yellow solid; Rf: 0.54 (EtOAc/
n-hexane, 1:3); M.p. 92 °C (Lit. 92 °C )[46]; IR (KBr): ύmax (cm–1) 2949 (=C-H), 1654 (C=O);
1H-NMR (CDCl3, 400 MHz, δ in ppm): 2.94 (2H, t, J = 7.2 Hz, H3), 3.10 (2H, t, J = 7.2 Hz, H4), 3.75
(3H, s, OMe), 6.69 (1H, s, H1′), 6.82 (2H, d, J = 6.8 Hz, H3′′), 7.15 (2H, d, J = 6.8 Hz, H2′′), 7.24–7.35 (2H,
13
m, H5, H7), 7.44 (1H, ddd, J = 7.2, 7.2, 1.8 Hz, H6), 7.90 (1H, dd, J = 7.2, 1.8 Hz, H8); C-NMR
(75 MHz, CDCl3, δ in ppm): 27.8, 28.7 (t, C3, C4), 66.1 (q, OCH3), 111.6 (s, C1′′), 121.8 (2×, d, C3′′),
127.9 (2×, d, C2′′), 125.4, 127.2, 128.5, 131.0, 132.7, (d, C5, C6, C7, C8, C1′), 134.0 (s, C2), 142.9, 147.8
(s, C4a, C8a), 187.4 (s, C1); EI-MS (m/z, amu): 264 [M]+ (100%), 236 [M − CO]+ (88%).
2-(3′′-Chlorobenzylidene)-3,4-dihydro-2H-naphthalen-1-one (5m): Dull-brown solid; Rf: 0.56
(EtOAc/n-hexane, 1:3); M.p.: 71–74 °C (Lit. 72 °C )[46]; IR (KBr): ύmax (cm–1) 2948 (=C-H), 1662

Molecules 2013, 18
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1
(C=O), 785 (C-Cl); H-NMR (CDCl3, 300 MHz, δ in ppm): 2.98 (2H, t, J = 7.2 Hz, H3), 3.08 (2H, t,
J = 7.2 Hz, H4), 6.81 (1H, s, H1′), 7.18–7.24 (3H, m, H2′′, H4′′, H5′′), 7.33-7.47 (4H, m, H5-H7, H6′′), 7.86
13
(1H, d, J = 7.2 Hz, H8); C-NMR (75 MHz, CDCl3, δ in ppm): 27.2, 28.7 (t, C3, C4), 123.1, 124.2,
127.3, 128.4, 129.6, 133.1, 133.6, 133.8 (d, C5, C6, C7, C8, C2′′, C4′′, C5′′, C6′′), 134.4, 135.8, 137.5,
137.8, 148.3 (s, C2, C1′′, C3′′, C4a, C8a), 187.3 (s, C1); EI-MS (m/z, amu): 268, 270 [M]+ (38, 12%), 240,
242 [M − CO]+ (18, 7).
(E)-2-(2′′-Chloro-5′′-nitrobenzylidene)-3,4-dihydronaphthalen-1(2H)-one (7a): Off-white solid; Rf: 0.57
(EtOAc/n-hexane, 1:3); M.p.: 97 °C (Lit. 97 °C )[47]; IR (KBr): ύmax (cm–1) 2968 (=C-H), 1681 (C=O),
1519 (N=O), 738 (C-Cl); 1H-NMR (300 MHz, CDCl3, δ in ppm): 2.99 (4H, s, H3, H4), 7.24 (1H, m, H5),
7.38 (1H, t, J = 7.2 Hz, H7), 7.51 (1H, t, J = 7.2 Hz, H6), 7.62 (1H, d, J = 8.8 Hz, H8), 7.82 (1H, s, H1′),
8.14-8.19 (3H, m, H3′′, H4′′& H6′′); 13C-NMR (75 MHz, CDCl3, δ in ppm): 24.2, 28.4 (t, C3, C4), 123.5,
123.8, 126.4, 128.5, 128.9, 129.4, 132.5, 133.6 (d, C5-C8, C1′, C3′′, C4′′, C6′′), 136.4, 136.8, 137.3, 137.5,
139.4, 143.4 (s, C2, C4a, C8a, C1′′, C2′′, C4′′), 187.8 (s, C1); EI-MS (m/z, amu): 315, 317 [M]+
(21, 6%), 280 [M − Cl]+ (81%).
4. Conclusions
The higher yields (72%–97%) of chalcones are obtained by SSA-mediated coupling over other
reported strategies. Furthermore, the slightly lower yields of the hydroxyl substituted chalcones from
solvent free NaOH mediated condensation makes SSA the method of choice for the synthesis of chalcones.
Acknowledgments
The authors are obliged to the Higher Education Commission, Government of Pakistan for generous
support of a research project (HEC 20-809), fellowship to Aeysha Sultan (074-141-Ps4-435), IRSIP
award and financial assistance for ESI MS, LR EIMS & NMR-analyses. The authors are also grateful
to the Department of Physics, University of Sargodha for single crystal XRD analyses.
Conflicts of Interest
The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds 3a–o, 5a–m and 7a–b are available from the authors.
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