One-pot two-step synthesis of 3-iodo-4-aryloxy coumarins and their Pd/C-catalyzed annulation to coumestans

Article abstract of DOI:10.1039/c7ra12419h

An efficient protocol for the synthesis of various coumestans from the intramolecular annulation of 3-iodo-4-aryloxy coumarins through C-H activation has been developed. When 3-iodo-4-aryloxy coumarins were treated with 10% Pd/C (0.3 mol% Pd) in the presence of sodium acetate, the corresponding coumestans were produced in good to excellent yield. Reusability of the palladium catalyst was investigated in up to three consecutive cycles and it was found that the yield of the reaction was almost unaltered. Sequential iodination and O-arylation of 4-hydroxy coumarins leading to the 3-iodo-4-aryloxy coumarins were also achieved in a one-pot two-step process starting from aryl iodides in high yield. Pivalic acid was revealed to be the most effective additive for the later method to produce 3-iodo-4-phenoxy coumarins. Different functional groups bearing electron-donating as well as withdrawing groups are also tolerant to the reaction conditions.

Full text of DOI:10.1039/c7ra12419h

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One-pot two-step synthesis of 3-iodo-4-aryloxy
coumarins and their Pd/C-catalyzed annulation to
coumestans†
Cite this: RSC Adv., 2018, 8, 7716
*
Niranjan Panda
and Irshad Mattan
An efficient protocol for the synthesis of various coumestans from the intramolecular annulation of 3-iodo-
4-aryloxy coumarins through C–H activation has been developed. When 3-iodo-4-aryloxy coumarins were
treated with 10% Pd/C (0.3 mol% Pd) in the presence of sodium acetate, the corresponding coumestans
were produced in good to excellent yield. Reusability of the palladium catalyst was investigated in up to
three consecutive cycles and it was found that the yield of the reaction was almost unaltered. Sequential
iodination and O-arylation of 4-hydroxy coumarins leading to the 3-iodo-4-aryloxy coumarins were also
achieved in a one-pot two-step process starting from aryl iodides in high yield. Pivalic acid was revealed
to be the most effective additive for the later method to produce 3-iodo-4-phenoxy coumarins.
Different functional groups bearing electron-donating as well as withdrawing groups are also tolerant to
the reaction conditions.
Received 14th November 2017
Accepted 11th February 2018
DOI: 10.1039/c7ra12419h
rsc.li/rsc-advances
On the other hand, ring closure of preformed aryl-coumarin
ether through C–C bond formation has been employed
Introduction
successfully (Scheme 1, path b) to construct the coumestan
skeletal framework. In 1990, Laschober and Kappe6 rst re-
ported the PdCl2 (0.5 equiv.) mediated synthesis of coumestans
(3 examples) from 4-aryloxy-3-iodocoumarins in triethyl amine.
Later, in 2013, Kapdi and co-workers7 employed palladacycles to
construct the furan ring through C–H functionalization of
substituted 4-(2-bromophenoxy)-coumarins. Recently, Cheng
et al. developed a Pd(OAc)2-catalyzed one-pot, two-step cycliza-
tion reaction of iodobenzene with coumarin to produce the
corresponding coumestan.8 McGlacken9 developed an intra-
molecular direct arylation approach using pre-halogen func-
tionalized 4-aryloxy coumarins as substrates. Very recently,
McGlacken10a and Xu10b independently reported Pd(OAc)2-cata-
lyzed cross-dehydrogenative coupling reaction of 4-phenoxy
coumarins to access coumestans in the presence of excess
amount of expensive silver salt. Despite largely improved effi-
ciency, these methodologies generally requires the use of
ligands, precious transition metal catalyst such as Pd(OAc)2,
PdCl2, AgOAc, Ag2O and multi-step strategy to the starting
materials (e.g. 4-aryloxy coumarin and 3-halo 4-aryloxy
coumarin). In this context, development of a stable and less
expensive catalytic system to achieve these biologically potent
tetracycles under ligand-free conditions is admirable from the
synthetic point of view. In continuation of our recent interest in
the synthesis of heterocycles,11 herein, we report a more
convenient ligand-free and less expensive catalytic method
using Pd supported on charcoal (i.e. Pd/C) as a heterogeneous
catalyst for the successful synthesis tetracyclic coumestans
(path c) through C–H activation reaction. It is noteworthy that
Benzofuran-fused coumarins, commonly called coumestans,
constitute a class of plant products (secondary metabolites)
found abundantly in split peas, pinto beans, lima beans, alfalfa
and clover sprouts. Coumestans including coumestrol, wede-
lolactone, isoglycyrol, psoralidin, erosnin, medicagol, and many
others exhibit diverse biological properties such as phytoestro-
genic, antioxidant, antihepatotoxic, antifungal and antitumor
activities (Fig. 1).1 Further, these compounds serve as chemo-
preventive agents for breast and prostate cancers.2 Consid-
ering their physiological and pharmacological potential, it is
desirable to develop more efficient synthetic strategies to ach-
ieve newer coumestans for pharmaceutical research.3 Among
the reported synthetic protocols, transition metal mediated
assembly of furan nucleus of the fused tetracyclic scaffold is
emerged to be the most promising. Annulation of 3-aryl-4-
hydroxyl coumarins through oxidative C–O bond formation
(Scheme 1, path a) is a classical pathway to achieve coume-
stans.4 Zhao and co-workers developed a FeCl3-mediated dehy-
drogenative C–O cross-coupling protocol to achieve
coumestans.5 However, limited substrate scope, multistep
sequence to access starting material and use of stoichiometric
excess of catalyst which in-turn is wasteful, oen vitiates its
large scale use.
Department of Chemistry, National Institute of Technology, Rourkela, Odisha-769008,
India. E-mail: npanda@nitrkl.ac.in; niranjanpanda@gmail.com
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c7ra12419h
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limitations. Not only stoichiometric excess (10 equiv. in most
cases) of oxidants were employed for the synthesis of aryl
iododiacetates, tedious purication procedure resulting in poor
yield of the reagent. Therefore, we motivated to access o-iodo-
diaryl ethers (e.g. 3aa) directly in a one-pot two-step method
using readily available aryl iodide for both arylating as well as
iodinating agent. Notably, aryliodide-catalyzed oxidative C–C
and C–N bond formation reactions leading to heterocyclic
carbazoles, benzimidazoles, indoles and phenanthridinones
were reported in the literature.14 It has been proposed that aryl
iodide oxidized by the terminal oxidant (e.g. mCPBA, K2S2O8,
Oxone®, etc.) in hexaouro isopropanol (HFIP) to hypervalent
iodine(III) species, which served as the catalyst for the said
oxidative transformations under metal-free conditions. Con-
trastingly, use of in situ generated hypervalent iodine species for
tandem iodination and O-arylation is not much literature
precedent.
Fig.
coumestans.
1 Examples of biologically potent naturally occurring
the precursor for coumestans i.e. o-iodocoumarin-aryl ethers
were also achieved in a more simplied process directly from
the reaction of coumarins and aryl iodides in one-pot.
Our optimization studies commenced with 4-hydroxy
coumarin 2a and iodobenzene (1a) by the screening of tandem
O-arylation and ortho-iodination promoters in one-pot (Table 1).
Firstly, iodobenzene was treated with oxidant at 50 ꢀC over
a period of 5 h for the formation of hypervalent iodine reagent,
and then 2a was added and reuxed for overnight for sequential
iodination and O-arylation reaction. We began our study with
the use of an oxidants such as Oxone®, K2S2O8, NaIO4, TBHP
and NaBO3$H2O for in situ oxidation of iodobenzene and
subsequent transformation to 3-iodo 4-aryloxy coumarin (3aa).
Unfortunately, in all such cases the desired product 3aa was not
observed (entries 1–5). Interestingly, when the reaction was
conducted in the presence of mCPBA (3 equiv.) in polar solvent
like 1,4-dioxane, 3aa was obtained in 38% yield (entry 6). When
the reaction was carried out in the non-polar solvent such as
toluene under reux, 3aa was obtained in 45% yield (entry 7).
Gratifyingly, the yield of the desired product was further
enhanced up to 70% by conducting the reaction in the presence
of acetic acid as an additive (entries 8 and 9). Effect of other
additives in the above reaction was also examined (entries 10–
13). In the presence of the base such as Na2CO3, no desired
product was achieved. Signicantly, when the reaction was
performed in the presence of 3 equiv. of pivalic acid (as an
additive) and mCPBA (3 equiv.) in toluene, 3aa was produced in
90% yield (entry 13). To realize the solvent effect on reaction
yield, other solvents (such as DMF, DMSO, CH3CN and DCE)
were screened (entries 14–18) and none of the cases the better
result was produced. While attempting to reduce the concen-
trations of iodobenzene and oxidant towards the development
of a cost-effective method, we noticed that 1 equiv. of iodo-
benzene reacts with 4-hydroxy coumarin (1 equiv.) in the pres-
ence of 1 equiv. of mCPBA and pivalic acid (3 equiv.) in toluene
affords 3aa in 45% yield (entry 19). The increase in the
concentration of iodobenzene and mCPBA to 1.5 equiv. each,
produces 3aa in 68% yield (entry 20). Further raising the oxidant
concentration to 2 equiv., 3aa was achieved in 88% yield (entry
21). Additionally, the effect of inert atmosphere for the reaction
was not realised as the yield of the reaction was unchanged both
in the presence of air as well as nitrogen atmosphere.
Results and discussion
We initiated our work with the development of an amicable
protocol for the synthesis of 3-iodo-4-aryloxy coumarin (3aa)
from 4-hydroxy coumarin (2a) using in situ generated hyper-
valent iodine for intramolecular annulation. Note worthy that
hypervalent diaryliodonium salts are typically used for selective
O-arylation reactions.12 However, use of diaryliodonium salt
causes the loss of an equimolar amount of expensive iodo-
benzene impedes its large-scale utility. On the other hand,
hypervalent iodine reagent such as phenyl iododiacetate (PIDA)
could be employed for sequential ortho-iodination and O-ary-
lation reactions.13 Notably, iodonium salts are produced in such
methods; that subsequently undergo phenyl migration leading
to ortho-iodo-O-phenyl arene. Despite of remarkable success of
the reaction with PIDA, similar reactions with other substituted
hypervalent iodine derivatives always end with a poor result.
Indeed, preparation of such substituted aryl iododiacetates for
tandem iodination/arylation is oen associated with certain
Scheme 1 Transition metal catalyzed routes to coumestans.
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Table 1 Optimization of reaction conditiona
Entry
Oxidant (equiv.)
PhI (equiv.)
Additive (3 equiv.)
Solvent
% yieldb
1
2
3
4
5
6
7
8
Oxone (3)
NaIO4 (3)
K2S2O8 (3)
TBHP (3)
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
—
—
—
—
—
—
—
AcOH
AcOH
TsOH
TFA
K2CO3
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
AcOH
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
Toluene
1,4-Dioxane
Toluene
Toluene
Toluene
Toluene
Toluene
CH3CN
MeOH
DCE
DMF
DMSO
Toluene
Toluene
Toluene
Toluene
n.d.
n.d.
n.d.
n.d.
n.d.
38
45
50
70
n.r.
60
n.r.
90
16
37
48
n.d.
n.d.
45
68
88
NaBO3$H2O (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (3)
mCPBA (1)
mCPBA (1.5)
mCPBA (2)
mCPBA (2)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
3
3
1
1.5
1.5
1.5
70
a
Reaction conditions: a mixture of oxidant and iodobenzene was heated at 50 ꢀC for 5 h in a sealed tube. Then, 2a was added and the reaction
mixture was reuxed. b GC yield.
Towards the mechanistic insight, we speculated that mCPBA group from iodo to oxygen to produce 3aa with the release of
could oxidize the iodobenzene to iodosobenzene (PhIO, A), PivOH. Indeed, when PhIO, prepared from the decomposition
which might be one of the key intermediates14a,b (Scheme 2). of PIDA with NaOH, was treated with 2a in the absence of pivalic
According to the previous report of Lei et al.,15 iodosobenzene acid, 3aa was formed fairly in low yield (40%), whereas similar
could react with pivalic acid to form B, which further gives rise reaction in the presence of pivalic acid, affords 3aa in excellent
to phenyl iododipivalate (PhI(OPiv)2) C in the presence of yield (90%). This observation suggests that pivalic acid serves as
PivOH. Indeed, the formation of C was evident from 1H NMR of a better ligating agent in the overall transformation. Addition-
the crude reaction mixture. For instance, the appearance of ally, when over oxidized iodine(V) derivative i.e. PhIO2, produced
signals at d 8.13–8.10 (m, 2H), 7.66–7.62 (m, 1H), 7.58–7.54 (m, from the disproportionation of PhIO, was treated with 2a both
2H) and 1.02 (s, 18H) in 1H NMR spectrum along with the in the presence of pivalic acid, 3aa was achieved in 42% whereas
signals for PhIO and PhIO2 conrms the formation of C. The similar reaction in the absence of the later results in 43% of 3aa.
reaction of C with 2a might produce the intermediate D. Thus, the in situ generated PhIO from PhI is the active inter-
Subsequent intramolecular aromatic nucleophilic attack of the mediate for sequential iodination and O-arylation of coumarins
oxygen atom causes the intramolecular migration of phenyl and not the PhIO2.
With the optimum reaction condition in hand, we next
explored the scope and generality of the tandem iodination and
O-arylation of coumarins (Scheme 3). Thus, the one-pot two-
step reaction of coumarins with different substitutions such
as –Me, –OMe, –Cl, –OBn, –NO2 etc. and PhI in the presence of
mCPBA produced 4-phenoxy 3-iodo coumarins in moderate to
good yield. Furthermore, aryl iodides bearing electron-donating
as well as withdrawing substituents (–Me, –Cl, –OMe, –OBn,
–NO2) coupled with 4-hydroxy coumarin to produce 3 in good
yield (63–82%) though the yield of reaction slightly diminished
Scheme 2 Plausible mechanism.
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remaining starting material. To suppress the undesired deha-
logenated product, alternative additives were tested for the
intramolecular annulation (Table 2). These experiments
revealed that other bases such as tBuOK, K2CO3, Cs2CO3 afford
5aa only (80% yield). Notably, aer several experimentations, it
has been realized that 1.5 equiv. of NaOAc in DMF at 130–140 ꢀC
produces 4aa predominantly in 93% yield. Furthermore,
replacing the solvent from DMF to DMA, 4aa was also isolated
in 94% yield without detection of any trace of dehalogenated
product 5aa.
In the course of optimization study as we are isolating some
amount of dehalogenated product, 5aa, it may be envisaged that
the annulation might be occurring through Pd/C-catalyzed C–C
bond formation through double dehydrogenative cross-
coupling in the presence of atmospheric oxygen. However,
when 5aa was treated with Pd/C following method C in the
presence of O2 atmosphere, no conversion occurred. With this
optimum reaction condition, we attempted the cyclization of
synthesized 3-iodo-4-aryloxy coumarins 3 to coumestans 4. To
our delight, in all cases, coumestans are produced in good to
excellent yield.
Recycle and reusability is a prime concern in heterogeneous
catalysis. Leaching and deactivation of catalyst oen encoun-
tered by resulting in the decrease in the rate of reaction and
hence yield of the isolated product. To investigate the reus-
ability and catalytic efficiency of the catalyst in annulation
process (3aa / 4aa), the workup process was modied slightly.
Aer completion of the reaction, yield was calculated by GC.
Then, to the reaction mixture another equiv. (0.1 mmol) of 3aa
and 1.5 equiv. of the base were added for the 2nd catalytic cycle.
Our effort to study the catalytic activity of Pd/C for three
consecutive cycles reveals that yield of the annulation process is
almost unaltered (cycle 1, 94%; cycle 2, 93%; and cycle 3, 92%
GC yield) though the rate of the reactions becomes sluggish.
Additionally, in another batch of reaction, aer 7 h, the catalyst
was ltered out under hot condition (61% yield from GC anal-
ysis) and the ltrate was heated at 140 ꢀC for the completion of
the reaction. Notably, aer 30 h the yield (60%) of the reaction
was not increased any more. This conrms that the leaching of
Pd from the catalyst (Pd/C) is not signicant for the completion
of the reaction. It may be assumed that the annulation reaction
proceeds through the usual oxidative addition to C–I bond,
ortho C–H insertion and nally reductive elimination cycle11c to
produce the coumestans 4. As leaching of Pd(0) is not occurring
signicantly to the solution, probably the overall trans-
formation is occurring on the surface of the catalyst. Alterna-
tively, aer 1st catalytic cycle (aer 16 h) the catalyst was ltered
and washed with methanol and dried in an oven for 3 h at
140 ꢀC (along with the lter paper). Next, the 2nd cycle was
performed using the catalyst obtained from the rst cycle (along
with the lter paper) in the presence of 1.5 equiv. of NaOAc at
140 ꢀC. Aer 24 h, the yield of the reaction was found to be 90%.
For cycle 3 and 4 similar procedure was repeated, and yield of
the annulation process was monitored aer 30 h (88% yield)
and 36 h (88% yield) respectively. This conrms that Pd/C is
truly a heterogeneous catalyst and can be reusable for C–C
coupling reactions to afford coumestans. Notably, the slight
Scheme 3 Synthesis of 4-aryloxy 3-iodo isocoumarins. aReaction
conditions: a mixture of 1 and mCPBA (2 equiv.) in toluene was heated
at 50 ꢀC for 5 h in a sealed tube. Then, 2 was added and the reaction
mixture was heated at 120 ꢀC for 12 h. bIsolated yield.
in the case of aryl halides containing an electron withdrawing
group over a period of 12 h, while prolonged heating for 24 h did
not improve the yield of the reaction.
Next, we turn our focus towards intramolecular annulation
of 4-aryloxy 3-iodocoumarins to coumestans using less expen-
sive reusable Pd-catalyst. Notably, earlier reports on coumestan
synthesis from 4-aryloxy 3-halocoumarins rely on the use of
PdCl2, Pd(OAc)2 and phospha-palladacycles in the presence of
expensive phosphorous-ligands. As a side note, to the best of
our knowledge there is no report for the cross-coupling reaction
of coumarin using heterogeneous Pd-catalyst. The quest for
commercially viable, highly active, recoverable, and reusable
palladium catalysts for the cross-coupling reaction allows us to
start our investigation with Pd on carbon (i.e. Pd/C) catalyst for
intramolecular C–C bond formation. Despite the low-cost,
stability and reusability, the catalytic activity of Pd/C was
underdeveloped except in catalytic hydrogenation. Moreover,
scattered precedents of Pd/C-catalyzed C–C coupling reactions16
gratify its catalytic potential. Thus, when 3-iodo-4-phenoxy
coumarin was reacted with NaOAc (3 equiv.), in the presence
ꢀ
of Pd/C catalyst in DMA at 130–140 C, tetracyclic coumestan
4aa was produced along with the dehalogenated product, 5aa.
Lowering of temperature to 110 ꢀC did not produce the product
4aa over a prolonged period of 24 h; rather the dehalogenated
product was produced in 35% yield with the recovery of
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Table 2 Synthesis of coumestans
Table 2 (Contd.)
Entry
1
Substrate (3)
Coumestan (4)
% yielda
Entry
10
Substrate (3)
Coumestan (4)
% yielda
3aa
94
3aj
91
2
3
4
3ab
3ac
3ad
94
85
90
11
12
13
3ba
3ca
3da
93
75
81
14
3ea
73
5
6
7
3ae
3af
3ag
79
78
96
a
Reaction conditions: [method C] a mixture of 3 (0.1 mmol), Pd/C
(10 wt%) (3 mg, 0.3 mol%), NaOAc (1.5 equiv.) in 3 mL of DMA at
140 ꢀC for 16 h.
lowering of obtained yield for the catalytic cycles from the GC
yield might be due to the handling loss, as the reaction was
performed in small scale.
8
9
3ah
3ai
89
89
Conclusions
In summary, an efficient one-pot two step strategy for the
synthesis of 3-iodo-4-aryloxy coumarin from the reaction of 4-
hydroxy coumarin and aryl iodide was developed. Both electron-
donating and withdrawing groups are observed to be inert
towards sequential ortho-iodination and O-arylation reaction.
Intramolecular annulation leading to a series of coumestans
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through C–C bond formation was achieved using commercially was collected by ltration and recrystallized from methanol to
viable Pd on charcoal (Pd/C) catalyst under ligand free condi- afford the corresponding 4-hydroxycoumarins 2e, 2f, 2g, 2h and
tions. Simple workup procedure and utilization of low-cost 2m.
reusable catalyst in the present method show promising
Synthesis of 4-hydroxy coumarins (2k, 2l).19 To an ice-cooled
synthetic potential in exploring biologically potent compounds solution of NaNO3 (0.52 g, 6.17 mmol) and concentrated
of the coumestan family. Application of this method for the sulfuric acid (20 mL) was added 4-hydroxycoumarin (1.00 g, 6.17
ꢀ
total synthesis of psoralidin, medicagol and isoglycyrol is going mmol) and stirred for 1 h at 0 C. Then, the reaction mixture
on in our laboratory.
was poured into ice-cooled water for precipitation. Upon ltra-
tion, the crude product was separated and recrystallized from
EtOAc/hexanes (7 : 3) to give the desired nitro compounds (2k
and 2l) as white crystalline solid.
Experimental
General information
General procedure for the synthesis of 3-iodo-4-aryloxy
coumarins
Unless otherwise noted, the reagents (chemicals) were
purchased from commercial sources and used without further
purication. The reactions were monitored by TLC, and the
residue was chromatographed on silica gel (Ranchem, India),
using an ethyl acetate–petroleum ether (60–80 ꢀC) mixture as
In a dry sealed tube, a mixture of aryl iodide (1.5 equiv.), m-
CPBA (2 equiv.), and pivalic acid (3 equiv.) in 3 mL of toluene
ꢀ
was added and stirred at 50 C, during which yellowish white
1
eluent. All NMR spectra were recorded on a 400 MHz (for H
solid was formed. Aer 5 h, 4-hydroxy coumarin (0.1 mmol) was
NMR) and 100 MHz (for 13C NMR) NMR spectrometer, and
chemical shis were expressed in d units relative to the TMS
signal as an internal reference in CDCl3. Multiplicities are
indicated as s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet, when multiplicity is complex) for 1H NMR. Coupling
constants, J were reported in Hz. High-resolution mass spec-
trometry (ESI-HRMS) (Agilent 6520 Q-TOF) was used to deter-
mine the elemental composition.
ꢀ
added to the reaction mixture and heated at 120 C for 12 h.
Then, it was cooled to room temperature and 20 mL of water
was added and extracted with dichloromethane (3 ꢁ 15 mL).
The combined organic layer was washed with dilute sodium
bicarbonate (10%) solution (2 ꢁ 10 mL). Then, the solvent was
removed under reduced pressure, and the crude reaction
mixture was puried by column chromatography over silica gel
(60–120 mesh) using mixture of ethyl acetate and petroleum
ether as eluent to give 3-iodo-4-aryloxy coumarins.
General procedure for synthesis of 4-hydroxy coumarins
General procedure for the Pd/C-catalyzed synthesis of
coumestans
Synthesis of 4-hydroxy coumarins (2a, 2b, 2c, 2d, 2i, 2j).17
A
mixture of phenol (10 mmol), malonic acid (10 mmol), ZnCl2 (30
mmol) and POCl3 (30 mmol) was stirred at 60 ꢀC. Aer 30 h, the
reaction mixture was cooled to room temperature and poured
into cold water (50 mL) during which precipitation occurred.
The precipitate ltered and washed with water 4–5 times. Then,
it was dissolved in 1 N NaOH solution (50 mL) and the insoluble
suspension was removed by ltration. The ltrate was acidied
further with concentrated HCl, and the precipitate was collected
by ltration. The crude product was recrystallized using meth-
anol to afford 2a, 2b, 2c, 2d, 2i, 2j and were used for the next
step directly without further characterization.
To a mixture of 3-iodo-4-aryloxy coumarins (0.1 mmol) and
NaOAc (0.15 mmol, 1.5 equiv.) in DMA (3 mL) was added 3 mg
(0.3 mol%) of Pd/C (10 wt%) and the reaction mixture was
heated at 130–140 ꢀC for 16 h. Aer completion of the reaction
(monitored by TLC), it was cooled to room temperature and
poured into water (10 mL). Then, the product was extracted with
ether (3 ꢁ 15 mL), and solvent was removed by rotary evapo-
rator. The crude product was puried by column chromatog-
raphy over silica gel (60–120 mesh) using a mixture of ethyl
acetate and petroleum ether as eluent to afford the coumestans.
Synthesis of 4-hydroxy coumarins (2e, 2f, 2g, 2h, 2m).18
mixture of phenol (10 mmol), acetic acid (40 mmol) and ZnCl2
A
Reusability study
(10 mmol) was heated to reux for 5–6 h. Then, it was allowed to To a mixture of 3aa (0.5 g, 1.37 mmol) and NaOAc (168.5 mg,
cool to room temperature and poured into cooled water. The 2.05 mmol) in DMA (7 mL) was added 41 mgꢀof Pd/C (10 wt%)
organic component was extracted by ethyl acetate, dried over and the reaction mixture was heated at 140 C for 16 h. Aer
anhydrous sodium sulphate and concentrated under reduced completion of the reaction (monitored by TLC), it was cooled to
pressure. The crude reaction mixture was puried by column room temperature and sampling was made for GC analysis,
chromatography to afford o-hydroxy acetophenone derivatives. which shows 95% yield of the product. For the 2nd cycle, to the
To a mixture of o-hydroxy acetophenone (5 mmol) and sodium original reaction mixture additional amount of 3aa (0.5 g, 1.37
hydride (60%) (15 mmol, 3 equiv.) in dry toluene (10 mL), mmol) and NaOAc (168.5 mg, 2.05 mmol) was added and heated
ꢀ
diethyl carbonate (5 mL) was added drop-wise at 0–5 C with at the same temperature for 20 h. Then, the reaction mixture
continuous stirring. Aer 1 h, the reaction mixture was heated was cooled to room temperature and yield of the reaction was
to 110 C for 12–20 h. Aer completion of the reaction (moni- calculated to be 93%. For 3rd cycle additional 0.5 g (1.37 mmol)
ꢀ
tored by TLC), it was allowed to cool to room temperature. Then, of 3aa and NaOAc (168.5 mg, 2.05 mmol) was added and heated
it was poured into an ice cold water. Acidication of the reaction at 140 ꢀC. Aer 30 h, the yield of the reaction was calculated to
mixture with dilute HCl resulted precipitation. The precipitated be 92% (by GC analysis). For the isolation of the product, the
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reaction mixture was poured into water (50 mL) and extracted Hz), 6.94 (d, 1H, J ¼ 2.8 Hz), 3.70 (s, 3H); 13C NMR (100 MHz,
with ether (3 ꢁ 25 mL). The combined organic layer was dried CDCl3) d 164.7, 159.7, 156.0, 155.2, 147.8, 130.0, 123.7, 121.0,
over anhydrous sodium sulphate and solvent was removed 117.9, 116.5, 116.0, 105.6, 80.8, 55.6. GC MS (EI, +ve) m/z (rela-
under reduced pressure. The crude product was puried by tive intensity) 393.9 ([M]+, 100%). HRMS (ESI) calcd for
column chromatography over silica gel (60–120 mesh) using
C
16H12IO4+ [M + H]+ 394.9780, found 394.9783.
a mixture of ethyl acetate and petroleum ether as eluent to
7-(Benzyloxy)-3-iodo-4-phenoxy-2H-chromen-2-one
(3ag).
1
ꢀ
afford the coumestan 4aa (894 mg from 1.5 g of 3aa in 92% over Redish solid (70% yield); mp 126–128 C; H NMR (400 MHz,
all yield from three consecutive batches). Following general CDCl3) d 7.47–7.32 (m, 9H), 7.15 (t, 1H, J ¼ 7.6 Hz), 7.00–6.94 (m,
procedure, the isolated yield for the 1st cycle is 306 mg from 3H), 6.84 (dd, 1H, J1 ¼ 8.8 Hz, J1 ¼ 2.4 Hz), 5.14 (s, 2H); 13C NMR
0.5 g of 3aa (94.4% yield) which is agreeable with the GC yield (100 MHz, CDCl3) d 165.0, 162.6, 159.9, 155.4, 155.1, 135.3,
(95%).
130.0, 128.7, 128.4, 127.4, 124.9, 123.5, 115.8, 113.5, 101.5, 75.9,
70.5. GC MS (EI, +ve) m/z (relative intensity) 470 ([M]+, 100%).
HRMS (ESI) calcd for C22H16IO4 [M + H]+ 471.0093, found
+
Analytical data
471.0079.
3-Iodo-4-phenoxy-2H-chromen-2-one6 (3aa). Pale yellow solid
6-(Benzyloxy)-3-iodo-4-phenoxy-2H-chromen-2-one
(3ah).
(88% yield); mp 138–139 ꢀC; 1H NMR (400 MHz, CDCl3) d 7.61 (t, White solid (70% yield); 1H NMR (400 MHz, CDCl3) d 7.41–7.29
1H, J ¼ 8 Hz), 7.55 (d, 1H, J ¼ 2 Hz), 7.56–7.33 (m, 3H), 7.26–7.12 (m, 8H), 7.25 (dd, 1H, J1 ¼ 8.8 Hz, J2 ¼ 2.8 Hz), 7.18 (d, 1H, J ¼
(m, 2H), 7.10–6.95 (m, 2H); 13C NMR (100 MHz, CDCl3) d 164.9, 7.6 Hz), 7.05–6.93 (m, 2H), 4.93 (s, 2H); 13C NMR (100 MHz,
159.6, 155.4, 153.3, 133.1, 130.1, 124.6, 123.8, 123.7, 116.8, CDCl3) d 164.6, 159.6, 155.2, 155.0, 147.9, 135.7, 130.1, 128.5,
116.1, 115.8, 80.5; MS (ESI, +ve) m/z (relative intensity) 386.9 ([M 128.1, 127.4, 123.7, 121.8, 117.9, 116.5, 115.9, 106.9, 81.0, 70.5.
+ Na]+, 100%).
GC MS (EI, +ve) m/z (relative intensity) 470 ([M]+, 100%). HRMS
3-Iodo-8-methyl-4-phenoxy-2H-chromen-2-one (3ab). Yellow (ESI) calcd for C22H16IO4+ [M + H]+ 471.0093, found 471.0090.
1
ꢀ
solid (85% yield); mp 130–132 C; H NMR (400 MHz, CDCl3)
3-Iodo-4-phenoxy-2H-benzo[h]chromen-2-one (3ai). Pale
1
d 7.47–7.41 (m, 4H), 7.18–7.07 (m, 2H), 7.00–6.94 (m, 2H), 2.53 yellow solid (72% yield); mp 188–190 ꢀC; H NMR (400 MHz,
(s, 3H); 13C NMR (100 MHz, CDCl3) d 165.3, 159.6, 155.6, 151.8, CDCl3) d 8.66–8.61 (m, 1H), 7.89–7.84 (m, 1H), 7.74–7.65 (m,
134.3, 130.1, 126.6, 124.2, 123.6, 121.6, 116.1, 115.9, 80.3, 15.7; 2H), 7.59 (d, 1H, J ¼ 8.8 Hz), 7.49 (d, 1H, J ¼ 8.8 Hz), 7.41–7.33
MS (ESI, +ve) m/z (relative intensity) 400.9 ([M + Na]+, 100%). (m, 2H), 7.16 (t, 1H, J ¼ 7.4 Hz), 7.04–6.97 (m, 2H); 13C NMR (100
+
HRMS (ESI) calcd for C16H12IO3 [M + H]+ 378.9831, found MHz, CDCl3) d 165.7, 159.8, 155.6, 151.3, 135.2, 130.2, 129.5,
378.9828.
127.9, 127.6, 124.7, 123.7, 122.7, 122.6, 119.0, 115.9, 112.0, 79.4.
3-Iodo-6-methyl-4-phenoxy-2H-chromen-2-one (3ac). White MS (ESI, +ve) m/z (relative intensity) 414.9 ([M + H]+, 100%).
1
+
solid (85% yield); mp 104–106 C; H NMR (400 MHz, CDCl3) HRMS (ESI) calcd for C19H12IO3 [M + H]+ 414.9831, found
ꢀ
d 7.42–7.30 (m, 5H), 7.20–7.12 (m, 1H), 7.01–6.94 (m, 2H), 2.34 414.9799.
(s, 3H); 13C NMR (100 MHz, CDCl3) d 165.1, 159.8, 155.4, 151.6,
2-Iodo-1-phenoxy-3H-benzo[f]chromen-3-one (3aj). White
1
134.6, 134.2, 130.1, 123.6, 123.3, 116.6, 116.1, 115.9, 80.4, 20.9; solid (65% yield); H NMR (400 MHz, CDCl3) d 8.84 (d, 1H, J ¼
MS (ESI, +ve) m/z (relative intensity) 400.9 ([M + Na]+, 100%). 8.4 Hz), 8.11 (d, 1H, J ¼ 8.8 Hz), 7.89 (dd, 1H, J1 ¼ 9.6 Hz, J2 ¼ 2
+
HRMS (ESI) calcd for C16H12IO3 [M + H]+ 378.9831, found Hz), 7.61–7.48 (m, 3H), 7.38–7.30 (m, 2H), 7.12 (t, 1H, J ¼ 7.4
378.9825.
Hz), 6.99 (d, 2H, J ¼ 7.6 Hz); 13C NMR (100 MHz, CDCl3) d 167.1,
6-Chloro-3-iodo-4-phenoxy-2H-chromen-2-one (3ad). White 160.3, 154.6, 154.2, 135.4, 130.9, 130.1, 129.2, 129.1, 127.4,
solid (70% yield); 1H NMR (400 MHz, CDCl3) d 7.60–7.53 (m, 126.3, 125.5, 123.6, 116.8, 116.1, 111.2, 82.1. MS (ESI, +ve) m/z
2H), 7.43–7.35 (m, 3H), 7.18 (t, 1H, J ¼ 7.2 Hz), 7.01–6.95 (m, (relative intensity) 414.9 ([M + H]+, 100%). HRMS (ESI) calcd for
2H); 13C NMR (100 MHz, CDCl3) d 163.9, 159.1, 155.0, 151.7,
C
19H12IO3+ [M + H]+ 414.9831, found 414.9826.
133.1, 130.2, 124.1, 123.1, 121.1, 118.3, 117.5, 116.0, 81.6; MS
3-Iodo-6-nitro-4-phenoxy-2H-chromen-2-one (3ak). White
1
(ESI, +ve) m/z (relative intensity) 420.9 ([M + Na]+, 100%), 436.8 solid (80% yield); mp 128–130 C; H NMR (400 MHz, CDCl3)
ꢀ
+
([M + K]+, 40%). HRMS (ESI) calcd for C15H9ClIO3 [M + H]+ d 8.51 (d, 1H, J ¼ 2.8 Hz), 8.47 (dd, 1H, J1 ¼ 6.8 Hz, J2 ¼ 2.8 Hz),
398.9285, found 398.9281.
7.58 (d, 1H, J ¼ 6.8 Hz), 7.44–7.38 (m, 2H), 7.24–7.19 (m, 1H),
3-Iodo-7-methoxy-4-phenoxy-2H-chromen-2-one
(3ae). 7.01–6.98 (m, 2H); d 13C NMR (100 MHz, CDCl3) d 163.9, 158.2,
Reddish solid (79% yield); 1H NMR (400 MHz, CDCl3) d 7.42 (d, 156.4, 154.8, 144.1, 130.4, 127.6, 124.6, 120.0, 118.2, 116.9,
1H, J ¼ 8.8 Hz), 7.39–7.31 (m, 2H), 7.15 (t, 1H, J ¼ 7.6 Hz), 6.99– 116.3, 81.9. HRMS (ESI) calcd for C15H8INO5+ [M + H]+ 408.9447,
6.93 (m, 2H), 6.89 (d, 1H, J ¼ 2.4 Hz), 6.63 (dd, 1H, J1 ¼ 9.2 Hz, J2 found 408.9442.
¼ 2.4 Hz), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3) d 165.1,
3-Iodo-8-methyl-6-nitro-4-phenoxy-2H-chromen-2-one (3al).
163.6, 160.0, 155.4, 155.2, 130.0, 124.9, 123.5, 115.8, 112.8, Off white solid (82% yield); mp 142–144 ꢀC; 1H NMR (400 MHz,
109.6, 110.5, 75.2, 55.8. GC MS (ESI, +ve) m/z (relative intensity) CDCl3) d 8.35–8.31 (m, 2H), 7.43–7.36 (m, 2H), 7.22–7.16 (m,
+
393.9 ([M]+, 100%). HRMS (ESI) calcd for C16H12IO4 [M + H]+ 1H), 7.02–6.98 (m, 2H), 2.62 (s, 3H); 13C NMR (100 MHz, CDCl3)
394.9780, found 394.9776.
d 164.3, 158.3, 154.9, 143.5, 130.4, 128.8, 128.3, 124.4, 117.5,
3-Iodo-6-methoxy-4-phenoxy-2H-chromen-2-one (3af). Col- 116.6, 116.2, 81.7, 16.0. HRMS (ESI) calcd for C16H10INO5+ [M +
ourless solid (68% yield); mp 146–148 C; H NMR (400 MHz, H]+ 422.9604, found 422.9599.
1
ꢀ
CDCl3) d 7.42–7.34 (m, 3H), 7.22–7.13 (m, 2H), 6.99 (d, 2H, J ¼ 8
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6,8-Dichloro-3-iodo-4-phenoxy-2H-chromen-2-one
RSC Advances
(3am).
4-Methyl-6H-benzofuro[3,2-c]chromen-6-one5 (4ab). White
White solid (78% yield); mp 192–194 ꢀC; 1H NMR (400 MHz, solid (94% yield); mp 166–168 C; H NMR (400 MHz, CDCl3)
CDCl3) d 7.66 (d, 1H, J ¼ 2.4 Hz), 7.48 (d, 1H, J ¼ 2.4 Hz), 7.43– d 8.19–8.13 (m, 1H), 7.91–7.85 (m, 1H), 7.68 (dd, 1H, J1 ¼ 2.6 Hz,
7.36 (m, 2H), 7.22–7.16 (m, 1H), 7.99–6.94 (m, 2H); 13C NMR J2 ¼ 1.6 Hz), 7.53–7.32 (m, 3H), 7.32 (t, 1H, J ¼ 7.6 Hz), 2.57 (s,
(100 MHz, CDCl3) d 163.6, 157.9, 154.9, 147.8, 133.0, 130.3, 3H); 13C NMR (100 MHz, CDCl3) d 160.4, 158.1, 155.5, 152.0,
1
ꢀ
130.1, 124.2, 123.0, 121.7, 118.5, 116.0, 82.4. HRMS (ESI) calcd 133.3, 127.1, 126.6, 125.1, 124.2, 123.5, 121.8, 119.5, 112.3,
+
for C15H7Cl2IO3 [M + H]+ 431.8817, found 431.8812.
111.7, 105.6, 16.22; MS (ESI, +ve) m/z (relative intensity) 273 ([M
3-Iodo-4-(p-tolyloxy)-2H-chromen-2-one (3ba). White solid + Na]+, 100%).
(82% yield); mp 148–150 ꢀC; 1H NMR (400 MHz, CDCl3) d 7.64–
2-Methyl-6H-benzofuro[3,2-c]chromen-6-one3j (4ac). White
7.52 (m, 2H), 7.43 (d, 1H, J ¼ 8 Hz), 7.25–7.17 (m, 1H), 7.15 (d, solid (92% yield); 1H NMR (400 MHz, CDCl3) d 8.16–8.10 (m,
2H, J ¼ 8 Hz), 6.90–6.84 (m, 2H), 2.34 (s, 3H); 13C NMR (100 1H), 7.80 (s, 1H), 7.66 (dd, 1H, J1 ¼ 6.8 Hz, J2 ¼ 2.4 Hz), 7.51–
MHz, CDCl3) d 165.1, 159.5, 153.3, 153.3, 133.2, 132.9, 130.4, 7.37 (m, 4H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3) d 160.0,
124.5, 123.8, 116.7, 116.2, 115.6, 80.1, 20.5. MS (ESI, +ve) m/z 158.3, 155.4, 151.8, 134.5, 133.0, 126.6, 125.1, 123.5, 121.8,
(relative intensity) 400.9 ([M + Na]+, 100%). HRMS (ESI) calcd for 121.5, 117.2, 112.2, 111.7, 105.7, 20.9; MS (ESI, +ve) m/z (relative
C
16H12IO3+ [M + H]+ 378.9831, found 378.9830.
4-(4-Chlorophenoxy)-3-iodo-2H-chromen-2-one (3ca). Yellow
intensity) 273 ([M + Na]+, 100%).
2-Chloro-6H-benzofuro[3,2-c]chromen-6-one3j (4ad). White
solid (65% yield); mp 84–85 ꢀC; 1H NMR (400 MHz, CDCl3) solid (90% yield); 1H NMR (400 MHz, CDCl3) d 8.20–8.14 (m,
d 7.63–7.57 (m, 1H), 7.50 (dd, 1H, J1 ¼ 8.0 Hz, J2 ¼ 1.6 Hz), 7.41 1H), 8.04 (d, 1H, J ¼ 2.4 Hz), 7.70 (dd, 1H, J1 ¼ 7.2 Hz, J2 ¼ 1.2
(d, 1H, J ¼ 8.0 Hz), 7.30 (dd, 2H, J1 ¼ 6.8 Hz, J2 ¼ 2.0 Hz), 7.27– Hz), 7.61–7.44 (m, 4H); 13C NMR (100 MHz, CDCl3) d 158.6,
7.19 (m, 1H), 6.91 (dd, 2H, J1 ¼ 7.2 Hz, J2 ¼ 2.0 Hz); 13C NMR 157.5, 155.6, 151.9, 131.9, 130.2, 127.2, 125.4, 123.1, 122.0,
(100 MHz, CDCl3) d 164.5, 159.2, 153.8, 153.2, 133.2, 128.8, 121.3, 118.9, 113.7, 111.9, 106.6; MS (ESI, +ve) m/z (relative
124.7, 123.5, 117.2, 116.8, 115.8, 115.3, 80.6. HRMS (ESI) calcd intensity) 293 ([M + Na]+, 100%).
for C15H9ClIO3+ [M + H]+ 398.9285, found 398.9251.
3-Methoxy-6H-benzofuro[3,2-c]chromen-6-one3j (4ae). White
(3da). solid (88% yield); mp 156–158 C; H NMR (400 MHz, CDCl3)
1
ꢀ
3-Iodo-4-(3-methoxyphenoxy)-2H-chromen-2-one
1
Gummy liquid (73% yield); H NMR (400 MHz, CDCl3) d 7.64– d 8.13–8.07 (m, 1H), 7.91 (dd, 1H, J1 ¼ 5.6 Hz, J2 ¼ 3.6 Hz), 7.67–
7.52 (m, 2H), 7.42 (d, 1H, J ¼ 8.4 Hz), 7.23–7.17 (m, 2H), 6.68 7.60 (m, 1H), 7.49–7.40 (m, 2H), 7.02–6.95 (m, 2H), 3.92 (s, 3H);
(dd, 1H, J1 ¼ 8.4 Hz, J2 ¼ 2.0 Hz), 6.58 (t, 1H, J ¼ 2.4 Hz), 6.49 13C NMR (100 MHz, CDCl3) d 162.9, 158.2, 155.4, 155.1, 130.2,
(dd, 1H, J1 ¼ 8.2 Hz, J2 ¼ 2.2 Hz), 3.80 (s, 3H); 13C NMR (100 126.0, 124.9, 123.5, 122.7, 121.3, 121.2, 112.9, 111.4, 105.7,
MHz, CDCl3) d 164.8, 161.1, 159.4, 156.3, 153.2, 132.9, 130.4, 101.3, 55.7. GC MS (EI, +ve) m/z (relative intensity) 266 ([M]+,
124.5, 123.7, 116.7, 116.1, 109.0, 107.8, 102.6, 80.5, 55.4. GC MS 100%).
(EI, +ve) m/z (relative intensity) 393.9 ([M]+, 100%). HRMS (ESI)
2-Methoxy-6H-benzofuro[3,2-c]chromen-6-one20 (4af). White
solid (78% yield); 1H NMR (400 MHz, CDCl3) d 8.17–8.11 (m,
+
calcd for C16H12IO4 [M + H]+ 394.9780, found 394.9778.
4-(3-(Benzyloxy)phenoxy)-3-iodo-2H-chromen-2-one
(3ea). 1H), 7.68–7.62 (m, 1H), 7.53–7.37 (m, 4H), 7.16 (dd, 1H, J1 ¼
Gummy liquid (71% yield); H NMR (400 MHz, CDCl3) d 7.63– 8.8 Hz, J2 ¼ 2.8 Hz), 3.94 (s, 3H); 13C NMR (100 MHz, CDCl3)
7.51 (m, 2H), 7.46–7.31 (m, 6H), 7.30–7.18 (m, 2H), 7.78 (dd, 1H, d 159.8, 158.2, 156.3, 155.4, 148.2, 126.7, 125.2, 123.5, 121.9,
J1 ¼ 8.4 Hz, J2 ¼ 2.0 Hz), 7.65–6.54 (m, 2H), 5.05 (s, 2H); 13C 120.2, 118.7, 112.7, 111.7, 106.0, 103.3, 55.9. GC MS (EI, +ve) m/z
NMR (100 MHz, CDCl3) d 164.8, 160.2, 159.4, 156.3, 153.2, 136.2, (relative intensity) 266 ([M]+, 100%).
1
133.0, 130.6, 128.5, 128.1, 127.4, 124.6, 123.7, 116.8, 116.1,
3-(Benzyloxy)-6H-benzofuro[3,2-c]chromen-6-one
(4ag).
109.9, 108.3, 103.4, 80.6, 70.2. GC MS (EI, +ve) m/z (relative White solid (96% yield); 1H NMR (400 MHz, CDCl3) d 8.19–8.10
intensity) 470 ([M]+, 100%). HRMS (ESI) calcd for C22H16IO4+ [M (m, 1H), 7.96–7.91 (m, 1H), 7.64–7.62 (m, 1H), 7.51–7.35 (m,
+ H]+ 471.0093, found 471.0090.
7H), 7.11–7.04 (m, 2H), 5.19 (s, 2H); 13C NMR (100 MHz, CDCl3)
3-Iodo-4-(4-nitrophenoxy)-2H-chromen-2-one (3fa). White d 161.9, 160.5, 158.2, 155.4, 155.1, 135.5, 128.6, 128.3, 127.4,
1
ꢀ
solid (63% yield); mp 150–152 C; H NMR (400 MHz, CDCl3) 126.0, 124.9, 123.5, 122.7, 121.4, 113.6, 113.0, 111.4, 106.0,
d 8.28 (dd, 2H, J1 ¼ 7.0 Hz, J2 ¼ 2.2 Hz), 7.72–7.63 (m, 1H), 7.52– 102.4, 70.5. GC MS (EI, +ve) m/z (relative intensity) 342 ([M]+,
+
7.45 (m, 2H), 7.32–7.24 (m, 1H), 7.11 (dd, 2H, J1 ¼ 7.0 Hz, J2 ¼ 100%). HRMS (ESI) calcd for C22H15O4 [M + H]+ 343.0970,
2.2 Hz); 13C NMR (100 MHz, CDCl3) d 163.8, 159.4, 158.9, 153.2, found 343.0969.
143.6, 133.6, 126.3, 124.9, 123.1, 117.1, 116.1, 115.5, 81.2. HRMS
(ESI) calcd for C15H9IO5+ [M + H]+ 409.9525, found 409.9527.
2-(Benzyloxy)-6H-benzofuro[3,2-c]chromen-6-one
White solid (89% yield); H NMR (400 MHz, CDCl3) d 8.13 (d,
(4ah).
1
6H-Benzofuro[3,2-c]chromen-6-one6 (4aa). White solid (94% 1H, J ¼ 7.2 Hz), 7.66 (d, 1H, J ¼ 7.2 Hz), 7.54–7.37 (m, 9H), 7.27–
yield); 1H NMR (400 MHz, CDCl3) d 8.15 (dd, 1H, J1 ¼ 6 Hz, J2 ¼ 2 7.20 (m, 1H), 5.18 (s, 2H); 13C NMR (100 MHz, CDCl3) d 159.7,
Hz), 8.05 (dd, 1H, J1 ¼ 7.6 Hz, J2 ¼ 2 Hz), 7.72–7.59 (m, 2H), 155.4, 155.3, 148.2, 136.0, 128.6, 128.2, 127.4, 126.6, 125.1,
7.55–7.39 (m, 4H); 13C NMR (100 MHz, CDCl3) d 159.9, 158.0, 123.4, 121.8, 120.7, 118.6, 117.9, 115.9, 112.7, 111.5, 105.9,
155.4, 153.6, 131.8, 126.7, 125.1, 124.5, 123.3, 121.8, 117.4, 104.7, 70.7. GC MS (EI, +ve) m/z (relative intensity) 342 ([M]+,
+
112.5, 111.6, 105.8; MS (ESI, +ve) m/z (relative intensity) 259 ([M 100%). HRMS (ESI) calcd for C22H15O4 [M + H]+ 343.0970,
+ Na]+, 100%).
found 343.0951.
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8H-Benzo[H]benzofuro[3,2-c]chromen-8-one (4ai). Yellow
solid (89% yield); mp 116–118 C; H NMR (400 MHz, CDCl3)
Conflicts of interest
1
ꢀ
d 8.70–8.62 (m, 1H), 8.21–8.15 (m, 1H), 8.00 (d, 1H, J ¼ 8.4 Hz), There are no conicts to declare.
7.91 (dd, 1H, J1 ¼ 7.2 Hz, J2 ¼ 2.4 Hz), 7.81 (d, 1H, J ¼ 8.8 Hz),
7.73–7.62 (m, 3H), 7.54–7.45 (m, 2H); 13C NMR (100 MHz,
CDCl3) d 160.9, 157.9, 155.5, 150.9, 134.8, 128.7, 128.0, 127.5,
Acknowledgements
Authors like to thank SERB (Ref. No. SB/S1/OC-21/2014) and
CSIR (Ref. No. 02(0278)/16/EMR-II), Government of India for
nancial support.
126.6, 125.1, 124.9, 123.5, 123.3, 122.7, 121.8, 117.4, 111.7,
107.8, 105.3. MS (ESI, +ve) m/z (relative intensity) 287 ([M + H]+,
100%). HRMS (ESI) calcd for C19H11IO3 [M + H]+ 287.0708,
+
found 287.0703.
8H-Benzo[f]benzofuro[3,2-c]chromen-8-one (4aj). Yellow
Notes and references
1
ꢀ
solid (91% yield); mp 176–178 C; H NMR (400 MHz, CDCl3)
d 9.23 (d, 1H, J ¼ 8.4 Hz), 8.26–8.19 (m, 1H), 8.03 (d, 1H, J ¼ 8.8
Hz), 7.95 (d, 1H, J ¼ 8 Hz), 7.85–7.77 (m, 2H), 7.67–7.59 (m, 2H),
7.59–7.48 (m, 2H); 13C NMR (100 MHz, CDCl3) d 161.2, 157.9,
155.3, 153.7, 133.0, 130.7, 130.2, 128.7, 127.4, 126.6, 126.2,
125.4, 125.2, 122.7, 121.7, 117.3, 111.6, 107.0, 106.0. MS (ESI,
+ve) m/z (relative intensity) 287 ([M + H]+, 100%). HRMS (ESI)
calcd for C19H11O3+ [M + H]+ 287.0708, found 287.0597.
8-Methyl-6H-benzofuro[3,2-c]chromen-6-one10a (4ba). White
solid (93% yield); 1H NMR (400 MHz, CDCl3) d 8.01 (dd, 1H, J1 ¼
8.0 Hz, J2 ¼ 1.6 Hz), 7.94 (s, 1H), 7.64–7.57 (m, 1H), 7.57–7.47
(m, 2H), 7.41 (t, 1H, J ¼ 7.6 Hz), 7.28 (dd, 1H, J1 ¼ 6.8 Hz, J2 ¼ 1.6
Hz), 2.52 (s, 3H); 13C NMR (100 MHz, CDCl3) d 159.9, 158.0,
153.8, 153.4, 135.0, 131.6, 127.8, 124.4, 123.3, 121.6, 121.5,
117.3, 112.6, 111.0, 105.5, 21.2. MS (ESI, +ve) m/z (relative
intensity) 273 ([M + Na]+, 100%).
8-Chloro-6H-benzofuro[3,2-c]chromen-6-one10a (4ca). White
solid (73% yield); 1H NMR (400 MHz, CDCl3) d 8.16–8.13 (m,
1H), 8.07–7.93 (m, 1H), 7.68–7.60 (m, 2H), 7.56–7.52 (m, 1H),
7.50–7.42 (m, 2H); 13C NMR (100 MHz, CDCl3) d 161.0, 157.7,
153.8, 153.8, 132.4, 131.1, 127.0, 124.8, 122.7, 122.0, 121.5,
117.6, 112.8, 112.3, 105.2.
9-Methoxy-6H-benzofuro[3,2-c]chromen-6-one5 (4da). White
solid (81% yield); 1H NMR (400 MHz, CDCl3) d 8.01–7.94 (m,
2H), 7.62–7.54 (m, 1H), 7.49 (d, 1H, J ¼ 8.0 Hz), 7.44–7.37 (m,
1H), 7.18 (d, 1H, J ¼ 2.0 Hz), 7.06 (dd, 1H, J1 ¼ 8.8 Hz, J2 ¼ 2.0
Hz), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3) d 159.5, 159.1,
158.0, 156.6, 153.0, 131.1, 124.4, 121.8, 121.3, 117.2, 116.3,
113.4, 112.6, 104.4, 96.5, 55.7. GC MS (EI, +ve) m/z (relative
intensity) 266 ([M]+, 100%).
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9-(Benzyloxy)-6H-benzofuro[3,2-c]chromen-6-one
(4ea).
White solid (73% yield); mp 154–156 ꢀC; 1H NMR (400 MHz,
CDCl3) d 8.04–7.95 (m, 2H), 7.99–7.55 (m, 1H), 7.53–7.36 (m,
7H), 7.26 (d, 1H, J ¼ 2.0 Hz), 7.16 (dd, 1H, J1 ¼ 8.6 Hz, J2 ¼ 2.2
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124.5, 121.9, 121.3, 117.3, 116.6, 114.2, 112.6, 97.8, 70.5. GC MS
(EI, +ve) m/z (relative intensity) 342 ([M]+, 100%). HRMS (ESI)
calcd for C22H15O4+ [M + H]+ 343.0970, found 343.0963.
4-Phenoxy-2H-chromen-2-one10a (5aa). 1H NMR (400 MHz,
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7.13 (m, 1H), 7.13–7.09 (m, 3H); 13C NMR (100 MHz, CDCl3)
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119.2, 116.7, 112.1. GC MS (EI, +ve) m/z (relative intensity) 238
([M]+, 100%).
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