Lewis acid promoted construction of chromen-4-one and isoflavone scaffolds via regio- and chemoselective domino Friedel-Crafts acylation/Allan-Robinson reaction

Article abstract of DOI:10.1039/c4ob01743a

A facile and efficient synthesis of chromen-4-one and isoflavone frameworks is achieved by the domino C-acylation/O-acylation/aldolization sequence. This operationally simple one-pot elegant strategy provides structurally unique chromen-4-ones and isoflavones directly from phenols via concomitant formation of multiple C-C and C-O bonds in a single operation. The outcomes of the buttressing effect, substituent dependence, and catalyst and solvent specificity during the course of the Friedel-Crafts acylation reactions are demonstrated and supported by fitting experiments.

Full text of DOI:10.1039/c4ob01743a

Organic &
Biomolecular Chemistry
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PAPER
Lewis acid promoted construction of chromen-
4-one and isoflavone scaffolds via regio- and
chemoselective domino Friedel–Crafts acylation/
Allan–Robinson reaction†‡
Cite this: Org. Biomol. Chem., 2014,
12, 9216
Tanmoy Chanda, Sushobhan Chowdhury, Suvajit Koley, Namrata Anand and
Maya Shankar Singh*
A facile and efficient synthesis of chromen-4-one and isoflavone frameworks is achieved by the domino
C-acylation/O-acylation/aldolization sequence. This operationally simple one-pot elegant strategy pro-
vides structurally unique chromen-4-ones and isoflavones directly from phenols via concomitant for-
mation of multiple C–C and C–O bonds in a single operation. The outcomes of the buttressing effect,
substituent dependence, and catalyst and solvent specificity during the course of the Friedel–Crafts acyla-
tion reactions are demonstrated and supported by fitting experiments.
Received 14th August 2014,
Accepted 16th September 2014
DOI: 10.1039/c4ob01743a
www.rsc.org/obc
Introduction
Chromones and isoflavones are of widespread chemical and
biological significance and are present in a large number of
molecules of medicinal importance.1 Chromones are often
very active as estrogen receptor modulators2a,b and thymidine
phosphorylase inhibitors.2c They have also been employed as
insecticidal2d and antifungal2e agents possessing high target
affinity and specificity. Substituted isoflavones serve as S-nitro-
soglutathione reductase (GSNOR) inhibitors3a and have been
shown to have osteogenic activity.3b The above biological pro-
perties have stimulated considerable interest toward the synthesis
of natural and unnatural analogues of isoflavones.4 Among the
reported methods for the synthesis of chromones the most
common one is the base catalyzed Allan–Robinson reaction of
ortho-acylphenols and carboxylic acid derivatives5 (Scheme 1).
In fact the most significant route to fabricate chromones is
actually a two-step process consisting of Friedel–Crafts acyla-
tion of the corresponding phenol followed by the Allan–Robin-
son reaction.
Scheme 1 Synthesis of chromones.
building blocks through a series of carefully choreographed
synthetic operations. Thus, a new cascade protocol to con-
struct chromone and isoflavone derivatives with pot, step, and
atom economy is highly desirable. As a part of our research
programme to devise new domino protocols for the synthesis
of biologically relevant molecules,6 here we describe the use of
phenols directly for the synthesis of chromones via the Lewis
acid promoted domino Friedel–Crafts acylation/Allan–Robin-
son reaction for the first time.
In recent years, complex molecular architectures of natural
products have been obtained from structurally simplified
The choice of substrates and reaction conditions in this
regard is the crucial factor as the Friedel–Crafts acylation reac-
tion is highly sensitive toward substituents.7 The substituent
dependence of this reaction was not properly justified in the
early literature8 as it was believed to be irreversible in nature.
However, later on the reversibility of this reaction was estab-
lished by a number of experiments disclosing the substituent
effects to a good extent.9 The reversibility of Friedel–Crafts acy-
lation via acetyl exchange was first examined by Gore and co-
workers.10 Herein, we discuss the effects of substituents,
scope, and limitations of the Lewis acid mediated Friedel–
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi-
221005, India. E-mail: mssinghbhu@yahoo.co.in; http:\\drmssinghchembhu.com;
Fax: (+91) 542-2368127
†This paper is dedicated to Prof. H. Ila on the occasion of her 70th birthday.
‡Electronic supplementary information (ESI) available: Elaborate reaction pro-
cedure; characterization data; scanned spectra of all the products. CCDC 932483
and 970761. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c4ob01743a
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Crafts acylation reaction. A variety of substrates and acylating ered unconsumed (Table 1, entry 1). Next, the above reaction
agents were employed, and it was observed that under varying was performed in nitromethane (CH3NO2) at 50 °C for 18 h.
conditions highly chemo- and regioselective outcomes were Notably, the reaction proceeded smoothly and an unexpected
achieved.
C–C coupled product 6a was obtained in 86% yield (Table 1,
entry 2). Neither our expected product 5ab nor the C-acylated
product 4-chloro-3,5-dimethyl-2-propionylphenol was formed.
A similar result was obtained when SnCl4 (2.5 mmol) was used
as the promoter in nitromethane (Table 1, entry 3). Formation
of 6a proceeds via a six-coordinated sigma-type EDA complex
of phenolic derivative 1a with AlCl3 or SnCl4 where nitro-
methane plays the dual role of solvent and oxidant.12 When
the above model reaction was carried out with 2.5 mmol of
SnCl4 under solvent-free conditions, interestingly, chemoselec-
tive O-acylation of 1a took place instead of C-acylation
affording 4-chloro-3,5-dimethylphenyl propionate 3ab in 92%
yield (Table 1, entry 5). Having found optimum reaction con-
ditions for chemoselective O-acylation, we next examined the
scope of this reaction by synthesizing some O-acylated deriva-
tives 3 (Table 2). The above SnCl4 mediated O-acylation of
phenols having a specific substitution pattern may be appli-
cable as an alternative to the other existing methods.13
Results and discussion
We started our investigation by taking 4-chloro-3,5-dimethyl-
phenol 1a and propionic acid 2b as the model substrates
under different Lewis acid mediated Friedel–Crafts acylation
conditions11 (Table 1). Initially, a neat mixture of 1a (1 mmol),
2b (10 mmol), and anhydrous AlCl3 (2.5 mmol) was heated at
100 °C under an argon atmosphere. No reaction took place
even after 12 h of heating and the starting phenol 1a was recov-
Table 1 Attempted Friedel–Crafts acylation of 1aa
Next, a mixture of 1a (1 mmol) and 2b (10 mmol) was
treated with 2.5 mmol of TiCl4 under solvent-free inert con-
ditions. The workup of the reaction afforded the expected chro-
mone derivative 5ab14 (Fig. 1) in quantitative yield involving
C-acylation, O-acylation, and aldol condensation as key steps
(Table 1, entry 6). This unique result prompted us to explore
the scope of this TiCl4 promoted cascade reaction. In this
regard, various substituted phenols 1a–h and different α-sub-
stituted acetic acids 2a–h were selected as counter substrates
for the synthesis of chromen-4-ones and isoflavones 5.
Catalyst
(mmol)
Temp.
(°C)
Time
(h)
Productb
(yield)
Entry
Solvent
c
1
2
3
4
5
6
7
8
9
AlCl3 (2.5)
AlCl3 (2.5)
SnCl4 (2.5)
TiCl4 (2.5)
SnCl4 (2.5)
TiCl4 (2.5)
TiCl4 (2.5)
TiCl4 (1.5)
TiCl4 (0.3)
None
100
50
50
12
18
18
18
8
2
6
—
MeNO2
MeNO2
MeNO2
None
None
None
6a (86)
6a (82)
6a (45)
3ab (92)
5ab (96)
5ab (88)d
5ab (65)e
5ab (10) f
50
100
100
80
100
100
None
None
6
6
Out of a broad range of substituted phenols used, only the
phenolic derivatives substituted at both the meta-positions
(1a–f) were found to be capable of providing the desired
product chromen-4-ones 5. Propionic acid 2b, its higher homo-
a Reaction conditions: a mixture of 1a (1 mmol) and 2b (10 mmol)
with different Lewis acids was heated under an argon atmosphere.
b Isolated pure yield in %. c No reaction. d 10% of 1a was recovered.
e 30% of 1a was recovered. f 85% of 1a was recovered.
Table 2 SnCl4 mediated O-acylation of substituted phenols 1a
Entry
1
1
2
3
Entry
3
1
2
3
2
4
a Reaction conditions: a mixture of 1 (1 mmol), 2 (10 mmol), and SnCl4 (2.5 mmol) was heated at 100 °C under an argon atmosphere. b Isolated
pure yield.
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acetic acid 2a along with 1a under similar reaction conditions
gave an inseparable mixture of 6-chloro-2,5,7-trimethyl-4H-
chromen-4-one 5aa, 5′-chloro-2′-hydroxy-4′,6′-dimethyl aceto-
phenone15 4aa, and 3-acetyl-6-chloro-2,5,7-trimethyl-4H-
chromen-4-one14 7aa (Fig. 1) along with the unreacted 1a
(Scheme 2).
When the substrate 1b was treated with 2b under similar
optimized reaction conditions, surprisingly, only a trace of the
desired product 5bb was obtained along with O-acylated
product 3bb in 85% yield (Table 3, entry 13). This anomalous
result could be due to the buttressing effect of the large
bromine atom flanked by two methyl groups. Next, 1g and 1h
were treated separately with excess of 2b in the presence of
Fig. 1 ORTEP diagrams of 5ab and 7aa.
logues 2c–f, and substituted phenyl acetic acids 2g–i as reac-
tion partners were also tolerated well affording the desired
product 5 in high yields (Table 3, entries 1–12). However,
Table 3 Synthesis of chromen-4-ones and isoflavones 5a
Entry
1
1
2
Product
Entry
9
1
2
Product
2
3
10
11
4
5
12
13
6
7
8
14
15
a A mixture of 1 mmol of 1, excess of 2 (10 mmol) and 2.5 mmol of TiCl4 was heated at 100 °C under argon. b Isolated pure yield in %.
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The destabilizing steric factor is absent in intermediates
4gb and 4hb making them stable due to their intramolecular
hydrogen bonding. Thus, the equilibrium mentioned earlier is
not possible, therefore, substrates 1g and 1h provided the
expected single regioisomer of ortho-acylated product 4 (4gb
and 4hb, respectively) in quantitative yield. However, in the
case of substrate 1b only a trace of the desired domino product
5bb was obtained along with 85% of O-acylated product 3bb.
Here, the large size of the Br atom exerts a massive buttressing
effect17 that strongly disfavours the formation of ortho-C-acy-
lated intermediate 4bb, hence the equilibrium mentioned
earlier entirely moved towards the direction where the steric
crowding can be minimized and provided 3bb almost
exclusively.
Fascinatingly, when acetic acid 2a was used as the acylating
reagent, the desired chromone 5aa was obtained in trace (6%)
along with ortho-C-acylated product 4aa in 60% yield
(Scheme 2). While the substituent ‘R’ becomes ‘H’ instead of
‘Me’ or its sterically higher analogues (Scheme 3), destabiliza-
tion of the C–C bond between the aryl ring and the associated
acyl group rather decreased, stabilizing the intermediate 4aa to
some extent. Under similar reaction conditions SnCl4 might
not be able to trigger the condensation steps B and C men-
tioned in Scheme 3, hence only the O-acylated products were
obtained. These observations provided insight into the reac-
tion mechanism and the substituent dependent reversibility of
Friedel–Crafts acylation reaction. Suitable size and co-ordinat-
ing properties of TiCl4 facilitate the condensation steps (steps
B and C mentioned in Scheme 3) and the reaction advanced
forward towards formation of highly substituted chromone
frameworks 5 and thus making this domino protocol specific
to TiCl4.18
Scheme 2 Fate of acetic acid 2a in Friedel–Crafts acylation/Allan–
Robinson reaction.
TiCl4 under previously optimized conditions. The workup of
the reaction mixture furnished the ortho-acylated products
4gb16a and 4hb,16b respectively, in quantitative yields (Table 3,
entries 14 and 15).
The reversibility of Friedel–Crafts reaction, which is
somehow substituent dependent, has a key role in the above
domino reaction for the formation of chromen-4-ones 5
(Scheme 3). Initial C-acylation yielded ortho-acylated phenols
4, which are thermodynamically stable due to hydrogen
bonding. However, in the case of substrates 1a–1f intermediate
4 would become relatively unstable because the acyl group
suffers steric repulsion by the adjacent methyl group and by
its neighbouring substituent X. Consequently, the acyl group
becomes tilted from the plane of the aromatic ring, resulting
redundancy in resonance, thus making the bond between the
acyl group and the aromatic ring quite labile.17a Hence, 4,6-
disubstituted ortho-acyl phenol becomes relatively unstable
and an equilibrium between C-acylated product 4 and O-acy-
lated product 3 was established (Scheme 3). Intermediates 4
and 3 appear to have similar energy and are present side by
side in the reaction medium.9a Next, in situ O-acylation of 4
provided intermediate 4′, which is cyclized via aldol conden-
sation to give the desired chromen-4-ones 5. Compound 5
is planar hence steric destabilization is minimized to some
extent. As soon as the intermediate 4 is converted to 5, to
maintain the equilibrium, 3 is converted to 4 and the reaction
moves toward completion. As a control experiment and to
emphasize our statement about the reversibility between 3 and
4, we performed the reaction of 3ab (1 mmol) with excess of
2b (10 mmol) in the presence of 2.5 mmol of TiCl4 under the
optimized reaction conditions. As per our expectations, 5ab
was formed in 92% yield after 10 h of heating.
To validate our mechanistic hypothesis, we attempted to
synthesize the intermediate 4-chloro-3,5-dimethyl-2-propionyl-
phenol (4ab) via different strategies and further wished to
employ it as an initial substrate along with 2b to produce 5ab.
We succeeded to synthesize 4-halo-2-(1-hydroxypropyl)-3,5-
dimethylphenol 9 but failed to oxidize the hydroxyl group of
the secondary alcohol 9 to transform it to 4. Several different
reported methods of oxidation were performed but none was
found to be successful (Scheme 4; for detailed discussion, see
ESI‡). This observation again supported the presence of a
Scheme 4 Attempted strategy for the synthesis of C-acylated
product 4.
Scheme 3 Mechanism for the synthesis of chromen-4-ones 5 and 7.
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strong steric effect and the buttressing effect exerted by the needed using a mixture of EtOAc and hexane in an appropriate
methyl and halogen groups present on the phenyl ring of 9, proportion as the eluent to provide pure 3.
which provided the main obstacle to oxidize the sp3-C centre
4-Chloro-3,5-dimethylphenylpropionate
(3ab). 1H-NMR
of 9 to sp2-carbonyl carbon of 4 (Scheme 4).
(300 MHz, CDCl3) δ 6.81 (s, 2H), 2.59 (q, J = 7.5 Hz, 2H), 2.35
(s, 6H), 1.27 (t, J = 7.5 Hz, 3H); 13C-NMR (75 MHz, CDCl3)
δ 172.9, 148.3, 137.3, 131.5, 121.3, 27.6, 20.7, 8.9; HRMS
(ESI-TOF) of C13H11ClO2 (m/z) = 235.0504 [M + Na+] (calculated
= 235.0502).
Conclusions
4-Chloro-3,5-dimethylphenyl-2-phenylacetate (3ag). 1H-NMR
(300 MHz, CDCl3) δ 7.25–7.19 (m, 5H), 6.67 (s, 2H), 3.70 (s,
2H), 2.21 (s, 6H); 13C-NMR (75 MHz, CDCl3) δ 169.8, 148.2,
137.3, 133.2, 131.6, 129.1, 128.6, 127.2, 121.1, 41.2, 20.6;
HRMS (ESI-TOF) of C16H15ClO2 (m/z) = 275.0838 [M + H+] (cal-
culated = 275.0839).
In conclusion, we have designed and developed an operation-
ally simple, highly efficient, and straightforward method for
the synthesis of highly functionalized and structurally unique
chromone and isoflavone derivatives from phenols for the first
time. This one-pot domino protocol involves the Lewis-acid
promoted Friedel–Crafts acylation/Allan–Robinson reaction
creating two C–C and one C–O new bonds in a single oper-
ation. We also established the substituent dependent reversi-
bility of Friedel–Crafts acylation through experimental
observations. Furthermore, how the buttressing effect guided
the outcomes of this reaction is thoroughly assessed and sup-
ported by appropriate experiments. The scope and diversity of
the tolerated substrates in this work is rather broad in com-
parison with the reported ones. A plausible reaction mechan-
ism was proposed to account for the cascade reaction.
4-Bromo-3,5-dimethylphenylpropionate
(3bb). 1H-NMR
(300 MHz, CDCl3) δ 6.81 (s, 2H), 2.593 (q, J = 7.5 Hz, 2H), 2.38
(s, 6H), 1.27 (t, J = 7.2 Hz); 13C-NMR (75 MHz, CDCl3) δ 172.8,
149.0, 139.3, 123.9, 121.1, 27.6, 23.8, 8.9.
2,3,5-Trimethylphenylpropionate (3eb). 1H-NMR (300 MHz,
CDCl3) δ 6.83 (s, 1H), 6.65 (s, 1H), 2.62 (q, J = 7.5 Hz, 2H),
2.25–2.23 (m, 6H), 2.00 (s, 3H), 1.29 (t, J = 7.5 Hz, 3H);
13C-NMR (75 MHz, CDCl3) δ 172.8, 148.9, 137.9, 135.7, 128.2,
125.2, 119.7, 27.5, 20.6, 19.8, 11.8, 9.1; HRMS (ESI-TOF) of
C12H16O2 (m/z) = 193.1228 [M + H+] (calculated = 193.1229).
General procedure for synthesis of 5
Experimental section
A similar procedure as above for the synthesis of 3 was utilized
except in place of SnCl4, TiCl4 was used.
General experimental details
1H and 13C NMR spectra were recorded at 300 and 75 MHz,
respectively. Chemical shift (δ) values are given in parts per
million (ppm) with reference to tetramethylsilane (TMS) as the
internal standard. Coupling constant (J) values are given in
hertz (Hz). High resolution mass spectra were recorded using
the ESI method. Organic solvents were dried by standard
methods prior to use. Commercially obtained reagents were
used after further purification when needed. All these reac-
tions were monitored by TLC with silica gel coated plates.
Column chromatography was carried out whenever needed,
using silica gel of 100/200 mesh. A mixture of hexane–ethyl
acetate in appropriate proportion (determined by TLC analysis)
was used as the eluent.
6-Chloro-2,5,7-trimethyl-4H-chromen-4-one.19 (5aa). 1H-NMR
(300 MHz, CDCl3) δ 7.15 (s, 1H), 6.06 (s, 1H), 2.96 (s, 3H), 2.47
(s, 3H), 2.30 (s, 3H); 13C-NMR (75 MHz, CDCl3) δ 179.6, 163.9,
142.0, 138.0, 137.2, 132.3, 117.2, 111.8, 111.7, 21.8, 19.8, 18.0.
6-Chloro-2-ethyl-3,5,7-trimethyl-4H-chromen-4-one
(5ab).
1H-NMR (300 MHz, CDCl3) δ 7.12 (s, 1H), 2.97 (s, 3H), 2.70 (q,
J = 7.65 Hz, 2H), 2.44 (s, 3H), 2.00 (s, 3H), 1.30 (t, J = 7.65 Hz,
3H); 13C-NMR (75 MHz, CDCl3) δ 179.4, 163.8, 155.2, 141.4,
137.8, 131.7, 119.8, 117.0, 116.6, 25.2, 21.7, 18.0, 11.2, 9.7;
CCDC 932483; HRMS (ESI-TOF) of C14H15ClO2 (m/z)
251.0838 [M + H+] (calculated m/z = 251.0839).
=
6-Chloro-3-ethyl-5,7-dimethyl-2-propyl-4H-chromen-4-one
(5ac). 1H-NMR (300 MHz, CDCl3) δ 7.11 (s, 1H), 2.98 (s, 3H),
2.64–2.45 (m, 5H), 1.80–1.72 (m, 2H), 1.29–1.25 (m, 2H), 1.13
(t, J = 7.5 Hz, 3H), 1.04 (t, J = 7.5 Hz, 3H); 13C-NMR (75 MHz,
General procedure for the synthesis of 3
A mixture of 1 mmol of 1, excess of 2 (10 mmol), and CDCl3) δ 178.9, 162.9, 155.2, 141.3, 137.8, 131.7, 123.3, 121.3,
2.5 mmol of SnCl4 was heated at 100 °C under an argon atmos- 120.3, 117.0, 33.2, 21.7, 20.7, 18.0, 13.8, 13.7; HRMS (ESI-TOF)
phere for the stipulated period of time mentioned in Table 2 of C16H19ClO2 (m/z) = 279.1152 [M + H+] (calculated =
(completion of the reaction was monitored via TLC analysis). 279.1154).
As in some cases the boiling point of the initial substrate 2
6-Chloro-2-heptyl-3-hexyl-5,7-dimethyl-4H-chromen-4-one
was less than 100 °C, a cold circulatory bath fitted with a con- (5ad). 1H-NMR (300 MHz, CDCl3) δ 7.07 (s, 1H), 2.94 (s, 3H),
denser was used to minimize the evaporation of the concerned 2.61 (t, J = 7.5 Hz, 2H), 2.41 (broad, 5H), 1.73–1.63 (m, 2H),
substrate. After completion of the reaction, the residue 1.27–1.22 (broad, 15H), 0.86 (broad, 7H); 13C-NMR (75 MHz,
obtained was dissolved in ethyl acetate (100 mL) and washed CDCl3) δ 179.0, 163.3, 155.2, 141.3, 137.8, 131.7, 121.9, 120.2,
with 4% aqueous HCl (100 mL × 2) followed by water, dilute 116.9, 31.6, 31.4, 29.5, 29.3, 29.2, 28.9, 28.8, 27.3, 24.8, 22.6,
NaHCO3, and brine. Ethyl acetate was evaporated and the 22.5, 21.7, 18.1, 18.0, 14.0; HRMS (ESI-TOF) of C24H35ClO2
crude was purified by column chromatography whenever (m/z) = 391.2401 [M + H+] (calculated 391.2398).
9220 | Org. Biomol. Chem., 2014, 12, 9216–9222
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6-Chloro-5,7-dimethyl-2-nonyl-3-octyl-4H-chromen-4-one 155.3, 141.9, 137.9, 132.1, 118.9, 116.3, 115.7, 25.2, 21.5, 17.1,
(5ae). 1H-NMR (300 MHz, CDCl3) δ 7.11 (s, 1H), 2.98 (s, 3H), 15.1, 11.2, 9.7; HRMS (ESI-TOF) of C15H18O2 (m/z) = 253.1193
2.64 (t, J = 7.5 Hz, 2H), 2.45 (broad, 5H), 1.71–1.66 (m, 2H), [M + Na+] (calculated 253.1199).
1.27 (broad, 23H), 0.87–0.85 (broad, 7H); 13C-NMR (75 MHz,
2-Ethyl-3,5,7,8-tetramethyl-4H-chromen-4-one (5eb). 1H-NMR
CDCl3) δ 179.0, 163.3, 155.2, 141.3, 137.9, 131.7, 122.0, 120.3, (300 MHz, CDCl3) δ 6.86 (s, 1H), 2.78–2.68 (m, 5H), 2.32–2.29
117.0, 31.8, 31.4, 29.9, 29.4, 29.3, 27.3, 24.8, 22.6, 21.7, 18.1, (m, 6H), 2.00 (s, 3H), 1.33 (t, J = 7.5 Hz, 3H); 13C-NMR
14.0; HRMS (ESI-TOF) of C28H43ClO2 (m/z) = 447.3033 [M + H+] (75 MHz, CDCl3) δ 180.6, 163.6, 155.3, 140.8, 136.8, 128.7,
(calculated 447.3024).
6-Chloro-3-(2-chloroethyl)-2-(3-chloropropyl)-5,7-dimethyl-4H- of C15H18O2 (m/z) = 231.1381 [M + H+] (calculated 231.1385).
chromen-4-one (5af). 1H-NMR (300 MHz, CDCl3) δ 7.15 (s,
2-Ethyl-3,5,7,8-tetramethyl-4-oxo-4H-chromen-6-yl propio-
122.3, 118.8, 115.9, 25.2, 22.5, 20.0, 11.3, 9.4; HRMS (ESI-TOF)
1H), 3.79 (t, J = 6.3 Hz, 2H), 3.65 (t, J = 6.3 Hz, 2H), 3.00–2.90 nate (5fb). 1H-NMR (300 MHz, CDCl3) δ 2.73–2.64 (m, 7H),
(m, 7H), 2.47 (s, 3H), 2.62–2.21 (m, 2H); 13C-NMR (75 MHz, 2.35 (s, 3H), 2.16 (s, 3H), 2.00 (s, 3H), 1.35–1.25 (m, 6H);
CDCl3) δ 178.6, 163.4, 155.2, 142.1, 138.0, 132.3, 119.9, 118.4, 13C-NMR (75 MHz, CDCl3) δ 180.5, 172.4, 163.7, 153.1, 144.2,
117.0, 43.9, 43.3, 29.8, 28.9, 28.6, 21.8, 18.0; HRMS (ESI-TOF) 134.4, 128.2, 123.8, 119.1, 116.0, 27.3, 25.2, 13.8, 13.6, 11.8,
of C16H17Cl3O2 (m/z)
389.0816).
=
389.0810 [M
+
Na+] (calculated 11.2, 9.5, 9.2; HRMS (ESI-TOF) of C18H22O2 = 325.1410 [M +
Na+] (calculated 325.1410); HRMS (ESI-TOF) of C18H22O2 (m/z)
2-Benzyl-6-chloro-5,7-dimethyl-3-phenyl-4H-chromen-4-one = 325.1410 [M + Na+] (calculated 325.1410).
(5ag). 1H-NMR (300 MHz, CDCl3) δ 7.46–7.14 (m, 11H), 3.82
(s, 2H), 2.94 (s, 3H), 2.47 (s, 3H); 13C-NMR (75 MHz, CDCl3)
δ 178.7, 161.7, 155.2, 142.1, 138.4, 135.9, 133.1, 132.3, 131.0,
Acknowledgements
130.6, 128.6, 127.0, 124.9, 120.8, 117.3, 38.6, 21.8, 18.2; HRMS
(ESI-TOF) of C24H19ClO2 (m/z) = 375.1153 [M + H+] (calculated We gratefully acknowledge the generous financial support
375.1152).
from the Science and Engineering Research Board (grant no.
6-Chloro-2-(4-fluorobenzyl)-3-(4-fluorophenyl)-5,7-dimethyl- SB/S1/OC-30/2013) and the Council of Scientific and Industrial
4H-chromen-4-one (5ah). 1H-NMR (300 MHz, CDCl3) Research (grant no. 02(0072)/12/EMR-II), New Delhi, India.
δ 7.24–6.93 (m, 9H), 3.78 (s, 2H), 2.92 (s, 3H), 2.47 (s, 3H); T. C., S. K., and N. A. are thankful to UGC, New Delhi for their
13C-NMR (75 MHz, CDCl3) δ 178.3, 164.1, 163.5, 161.8, 160.8, research fellowship. Spectral help from Prof. Ganesh Pandey,
160.2, 155.2, 142.4, 138.4, 132.5, 132.3, 132.2, 131.5, 130.1, CBMR, Lucknow and Prof. Manas Ghorai and Prof. Sandeep
130.0, 128.7, 123.8, 120.5, 117.2, 115.7, 115.4, 37.4, 21.8, 18.0; Verma, IIT Kanpur is highly appreciated.
HRMS (ESI-TOF) of C14H17ClF2O2 (m/z) = 411.0964 [M + H+]
(calculated 411.0958).
6-Chloro-2-(3,4-dichlorobenzyl)-3-(3,4-dichlorophenyl)-5,7-
References
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