Diversity-oriented general protocol for the synthesis of privileged oxygen scaffolds: Pyrones, coumarins, benzocoumarins and naphthocoumarins

Article abstract of DOI:10.1039/c3ob40859k

A new general methodology for the synthesis of various functionalized privileged oxygen heterocyclic scaffolds, viz. pyrones, coumarins, and benzannulated coumarins, is developed. The synthesis proceeds through carbanion-induced ring transformation of lactones with various methylene carbonyl compounds followed by DDQ-mediated unprecedented oxidative cleavage of oxaylidenes intermediates. Studies of the mechanism of the conversions of oxaylidene intermediates into corresponding carbonyl compounds in the presence of DDQ revealed that the reactions took place via the formation of a Michael adduct instead of an intermolecular charge transfer complex. The methodology offers the fabrication of diverse privileged scaffolds with tolerance for many functional groups onto the oxygen heterocyclic molecular framework.

Full text of DOI:10.1039/c3ob40859k

Organic &
Biomolecular Chemistry
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Diversity-oriented general protocol for the synthesis of
privileged oxygen scaffolds: pyrones, coumarins,
benzocoumarins and naphthocoumarins†
Cite this: Org. Biomol. Chem., 2013, 11,
5239
Atul Goel,*a Gaurav Taneja,a Ashutosh Raghuvanshi,a Ruchir Kantb and
Prakas R. Maulikb
A new general methodology for the synthesis of various functionalized privileged oxygen heterocyclic
scaffolds, viz. pyrones, coumarins, and benzannulated coumarins, is developed. The synthesis proceeds
through carbanion-induced ring transformation of lactones with various methylene carbonyl compounds
followed by DDQ-mediated unprecedented oxidative cleavage of oxaylidenes intermediates. Studies of
the mechanism of the conversions of oxaylidene intermediates into corresponding carbonyl compounds
in the presence of DDQ revealed that the reactions took place via the formation of a Michael adduct instead
of an intermolecular charge transfer complex. The methodology offers the fabrication of diverse privileged
scaffolds with tolerance for many functional groups onto the oxygen heterocyclic molecular framework.
Received 26th April 2013,
Accepted 21st June 2013
DOI: 10.1039/c3ob40859k
www.rsc.org/obc
require expensive organometallic catalysts (Pd, Ru or Au),
harsh reaction conditions and often lead to substances with
Introduction
α-Pyrone, coumarin and their benzannulated scaffolds are key traces of toxic metal impurities.6,7 Herein we report a new pro-
structural motifs found in a large number of biologically tocol for the synthesis of various privileged heterocyclic
important natural alkaloids, isolated from an eclectic array of scaffolds through carbanion-induced ring transformation of
plant and marine sources.1,2 Owing to their interesting photo- flexible or rigid lactones followed by DDQ-promoted unprece-
physical properties3 and the broad range of pharmacological dented oxidative cleavage of oxaylidenes to their corresponding
activities4 associated with them, they come under the category carbonyl compounds.
of privileged scaffolds in medicinal chemistry. As a conse-
quence; numerous approaches to the synthesis of pyrones,
Results and discussion
coumarins and benzocoumarins have been reported either by
the conventional approaches5 or by procedures involving tran-
sition metal-catalyzed reactions.6,7
Over the last decade we have been exploring the reactivity of
2H-pyran-2-ones towards various C- and N-nucleophiles for
generating diverse molecular architectures suitable for biologi-
cal and material applications.8 We have recently demonstrated
an efficient synthesis of the partially hydrogenated oxa[5]heli-
cenes 1a, 2a and investigated their stereochemical behaviour
in collaboration with Bringmann and co-workers.9 In our
further efforts directed towards the oxidation of 9,10-dihydro-
7-oxa[5]helicene-8-ylidenylacetonitrile 2a to produce oxa[5]heli-
cene 3a with a higher inversion barrier, we reacted 2a (inver-
sion barrier 78.2 kJ mol−1) with 2 equiv. of 2,3-dichloro-5,6-
dicyano-1,4-quinone (DDQ) using benzene as a solvent. Under
this condition, we failed to obtain 3a. When we attempted
the reaction of 5,6,9,10-tetrahydro-7-oxa[5]helicene-8-ylidenyl-
acetonitrile 1a in dioxane using 4 equiv. of DDQ, we observed
the formation of two new products 4a and 5a on TLC under
UV exposure at 254 nm (Scheme 1). The structures of both the
compounds were assigned by analyzing the spectroscopic data.
The structure of 4a was unambiguously confirmed by single-
Undoubtedly these classical approaches play a crucial role
in the realm of natural and medicinal chemistry; however in
the era of high throughput screening and the rapid generation
of libraries of small molecules, chemists need to keep up their
pace to fulfil the demands of current research. Therefore new
efficient and general synthetic methods, which produce privi-
leged scaffolds such as α-pyrones, coumarins and benzocou-
marins under one set of reaction protocols, would be what is
needed today, especially when the reported procedures usually
aDivision of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute,
Lucknow, India. E-mail: atul_goel@cdri.res.in
bDivision of Molecular and Structural Biology, CSIR-Central Drug Research Institute,
Lucknow, India
†Electronic supplementary information (ESI) available: Copies of 1H and 13C
NMR of the compounds prepared, X-ray data (CIF, 4a and 12). CCDC 877580 and
877581. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c3ob40859k
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Table 1 Optimization of unusual transformation
Yielda (%)
Entry Solvent
DDQ (equiv.) Temp (°C) Time (h) 4a
5a
1
2
3
4
5
6
7
8
9
Dioxane
Dioxane
Dioxane
AcOH
AcOH
AcOH
MeCN
Acetone
THF
4
4
0
4
4
0
4
4
4
4
rt
rx
rx
rt
rx
rx
rt
rt
rt
rt
24
4
4
1
2
15
43
—
58
42
—
Trace
Trace
—
5
12
—
—
—
—
—
—
—
—
2
Scheme 1 Synthesis of dinaphthopyranone 4a.
24
24
24
24
crystal X-ray analysis (4a: CCDC no. 877580; Scheme 1). An 10
unusual chlorination of the ylidenic proton in 1a led to the
formation of 5a in minor yield. Few unexpected chlorinations
on different substrates have been reported earlier for DDQ-
mediated oxidation reactions.10 Interestingly the unexpected
chlorination of the ylidenic proton is possible, however, the
conversion of such an ylidenic group into corresponding car-
bonyl functionality promoted by DDQ has not been reported
in the literature prior to this study. These new observations
prompted us to investigate the possibility of using the DDQ for
the cleavage of the ylidenic double bond.
MeOH
—
a Isolated yield, rt means room temperature, rx means reflux.
The compounds 4a,b were further converted into their fully
aromatized products 4H-benzo[f]naphtho[2,1-c]chromen-4-ones
(11a,b) using an excess amount of DDQ (15 equiv.) in refluxing
benzene. Such dinaphthopyranones exist in configurationally
labile helimeric equilibrium and they are important chemical
scaffolds for the atroposelective synthesis of a broad range of
naturally occurring biaryls and axially chiral auxiliaries.11 The
classical approaches for the synthesis of dinaphthopyranones
Considering the fact that there are limited synthetic
methods for the preparation of dinaphthopyranones,11 we
thus focused our attention on optimizing the reaction con-
ditions for this unexpected transformation (Table 1). In order
to improve the yield of 4a, we investigated the reaction using
5,6,9,10-tetrahydro-7-oxa[5]helicene-8-ylidenylacetonitrile 1a
(0.2 mmol) and DDQ (0.8 mmol) by changing the reaction con-
ditions as mentioned in Table 1. No product was observed in
THF and MeOH (Table 1, entries 7 and 8) while only traces of
cleaved products were formed in acetonitrile and acetone at
room temp (Table 1, entries 5 and 6). When dioxane was
used as a solvent we isolated 4a in moderate yield (entries 1
and 2), together with a minor product 5a (see the ESI;
Scheme S1†).
However switching the solvent from dioxane to acetic acid
significantly increased the yield of 4a (entries 3 and 4) and
only 4a was isolated as the sole product. The best result was
obtained with 4 equiv. of DDQ in AcOH at room temperature
producing a 58% yield of 4a (entry 4). It is worth noting that in
the absence of DDQ, no reaction occurred suggesting the role
of DDQ in the given transformation (entries 3 and 6).
With the optimized conditions in hand, a series of substi-
tuted (Z)-2-(5,6-dihydro-1H-benzo[f]naphtho-[2,1-c]chromen-4-
(2H)-ylidene)acetonitriles9 (1a–f) was subjected to oxidative
cleavage using DDQ (4 equiv.) as an oxidant in acetic acid to
afford partially hydrogenated 4H-benzo[f]naphtho[2,1-c]chromen-
4-ones (4a–f) in good yields (Scheme 2).
Scheme 2 Synthesis of 4H-benzo[f]naphtho[2,1-c]chromen-4-ones 4 and 11.
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Scheme 3 Proposed mechanism for the oxidative cleavage of the ylidenic bond of 2a.
mainly involve palladium-catalyzed intramolecular Heck aryl-
ation using harsh reaction conditions and limited only to less
sterically hindered substrates.11 Our approach provides an easy
access to these interesting compounds under mild reaction
conditions and without using any transition metal catalysts.
In order to examine the reaction mechanism, a survey of the
literature reveals examples of carbon–oxygen adduct formation
through charge transfer complex between DDQ and aromatic
hydrocarbons, heterocycles, and olefins.12 Based on these
literature reports, we proposed two possible pathways for the
formation of 4a as depicted in Scheme 3, which revealed that
the formation of 4a may be explained via a nonradical mech-
anism (path I) or through a radical mechanism (path II). In
the nonradical mechanism (path I), a carbon–oxygen adduct
(A) may be formed by Michael addition of the 5,6,9,10-tetra-
hydro-7-oxa[5]-helicene-8-ylidenyl-acetonitrile 2a to the 2,3-
dichloro-5,6-dicyano-1,4-quinone (DDQ) followed by intramole-
cular cyclization involving methyne carbon and the nitrile
Fig. 1 The crystal structure of 12 showing the network of intermolecular
N–H⋯N and O–H⋯N interactions.
group of DDQ to produce intermediate B. This intermediate B temperature. The absorption spectra of the reaction mixtures
under acidic conditions may lead to intermediate C, which on (∼10−6 μM) in acetic acid were monitored at different time
further internalization would afford the final product 4a intervals (Fig. 2).
together with the formation of 3-amino-benzofuran 12. Our
Neither a coloured ICT complex nor any band in the range
presumption for the path I is supported by the isolation and of 500–700 nm was observed during the reaction.12 These
characterization of a final product 4a together with the benzo- results clearly suggested that the reaction follows non-ICT path
furan derivative 12, whose structure was unambiguously con- I to produce compounds 4a and 12.
firmed using X-ray analysis of the air-sensitive single-crystals
To further extend the scope of the above ring transform-
of 12 in acetonitrile (Fig. 1). It is worth noting that the for- ation and considering that 4-aryl-coumarins (neoflavones)
mation of diffraction quality crystals of 12 was largely depen- are ubiquitous structural units in a plethora of natural
dent on the acetonitrile solvent molecules, which formed products with interesting biological activities,13 we designed a
intermolecular hydrogen bonding with the NH2 group of the new protocol utilizing the reactivity of substituted resorcinols
furan ring. As soon as the solvent evaporates during the crystal 13 towards 2H-pyran-2-ones 14 in the presence of a base
growth, the crystals become opaque revealing the importance (Scheme 4). Thus reaction of commercially available sub-
of strong non-covalent interactions with acetonitrile solvent in stituted resorcinols 13 (R1, R2 = H, Me, Cl) and 6-aryl-4-(methyl-
the crystal formation.
thio)-2-oxo-2H-pyran-3-carboxylate14 14 in NaH/DMF afforded
Similarly a radical mechanism (path II) may be proposed methyl 2-(7-hydroxy-2H-chromen-2-ylidene)acetates 15 in good
via the formation of an intermolecular charge transfer (ICT) yields (up to 60–70%) as a mixture of geometrical isomers.
complex between 2a and DDQ followed by a single electron As depicted in Scheme 4, the reaction is possibly initiated by
transfer (SET),12 which on recombination may form a carbon– a Michael addition of a conjugate base of resorcinol generated
oxygen adduct (A). To check the possibility of a single electron in situ in the presence of a base, at C6 of the 6-aryl-4-
transfer (SET) mechanism (path II), we carried out an indepen- (methylthio)-2-oxo-2H-pyran-3-carboxylates 14 followed by ring
dent experiment by reacting 2a and DDQ in acetic acid at room opening to give intermediate I.
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Fig. 2 Absorption spectra of the reaction mixtures (∼10−6 μM) in acetic acid at
different time intervals.
This Michael intermediate I may undergo an intramole-
cular cyclization involving the carbonyl functionality and C4
center of 14 with the elimination of carbon dioxide and methyl
mercaptan to yield the (Z/E)-methyl 2-(7-hydroxy-2H-chromen-
2-ylidene)acetates 15 in good yields. Furthermore these
ylidenes 15a–f were converted to 4-aryl-7-hydroxy-coumarins
16a–f through oxidative cleavage using DDQ (2 equiv.) in
dioxane at 80 °C for 1–2 h. The formation of carbomethoxy-
substituted benzofuran 17 as a side product similar to the
product 12 confirmed the possible route I for obtaining the
coumarins 16a–f. Although numerous synthetic methodologies
for 4-aryl/heteroaryl-coumarins are reported, most of them
depend on organometal-catalyzed reactions via C–H or C–X
activation on a preformed coumarin nucleus.15 Our novel
methodology provides an easy access to 4-aryl-7-hydroxy-
coumarin derivatives under a transition-metal free environ-
ment using easily available precursors in good yields.
After successful demonstration of this methodology for the
preparation of 4-aryl-7-hydroxy-coumarins 16a–f, we extended
the methodology to the synthesis of benzocoumarins viz.
5,6-dihydro-2H-benzo[h]chromen-2-ones (19) and 2H-benzo[h]-
chromen-2-ones (20) (Scheme 5). To synthesize these com-
pounds, the requisite precursor methyl 2-(4-aryl-5,6-dihydro-
2H-benzo[h]chromen-2-ylidene)acetates 18a–c were prepared
according to improved methodology.16 Treatment of 18a–c
with DDQ (2 equiv.)/AcOH afforded the 4-aryl-5,6-dihydro-2H-
benzo[h]chromen-2-one 19a–c in moderate yields (46–52%).
The partially hydrogenated benzocoumarin 19a was aroma-
tized using DDQ in benzene at reflux temperature to afford
4-(4-bromophenyl)-8-methoxy-2H-benzo[h]chromen-2-one (20a)
in a 52% yield.
Scheme 4 Synthesis of 4-arylcoumaryl-2-ylidenes 15 and 4-arylcoumarins 16.
Experimental section) and converted to highly substituted
α-pyrones 24a–f through oxidative cleavage using DDQ
(2 equiv.)/AcOH at room temperature in 5–6 h (Scheme 6).
It is important to note that highly hindered 2-(6-isopropyl-
4-(4-methoxyphenyl)-3-methyl-5-phenyl-2H-pyran-2-ylidene)-
acetonitrile (23f) was successfully converted to the corres-
ponding carbonyl compound 6-isopropyl-4-(4-methoxyphenyl)-
3-methyl-5-phenyl-2H-pyran-2-one (24f) under the same reac-
tion conditions. This new methodology offers a general syn-
thesis of α-pyrones with four point diversity.
Finally, the synthesis of highly substituted α-pyrones
(24a–f) was explored as shown in Scheme 6. The precursors
functionalized 2H-pyran-2-ylidene-acetonitriles 23a–f were pre-
pared by reacting substituted 2H-pyran-2-ones 21a–f with sub-
stituted methylene carbonyl compounds 22a–f (see the
Conclusion
In summary, we have demonstrated a novel and general
synthesis of highly functionalized α-pyrones, coumarins and
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benzannulated coumarins through the ring transformation of
easily accessible lactones with various methylene carbonyl
compounds followed by unprecedented DDQ-mediated
oxidative cleavage of oxaylidene intermediates under mild
reaction conditions. Studies of the synthesis mechanism of
a benzonaphthocoumarin revealed that the reaction was
initiated through Michael addition as examined using UV-vis
absorption experiments. This methodology can be used for the
synthesis of a variety of oxygen heterocycles with flexibility of
substituents variation on to the molecular scaffolds. Interest-
ingly, this diversity-oriented synthetic protocol may be useful
to generate a small library of compounds for drug discovery
perspectives.
Experimental section
1H and 13C NMR spectra were taken on a NMR spectropho-
tometer at 400, 300 and 200 MHz. CDCl3 and DMSO-d6 were
used as the solvents. Chemical shifts are reported in parts per
million (δ-value) from Me4Si (δ = 0 ppm for 1H) as an internal
standard or based on the middle peak of the solvent (for
1
CDCl3, 7.26 ppm for H and 77.1 ( 0.1) ppm for 13C NMR; for
1
DMSO-d6, 2.5 ppm for H and 40.0 ppm for 13C NMR). Signal
Scheme 5 Synthesis of benzocoumarinyl-2-ylidenes 18 and benzocoumarins
19 and 20.
patterns are indicate as s, singlet; d, doublet; dd, double
doublet; t, triplet; m, multiplet. Coupling constants ( J) are
given in hertz. Infrared (IR) spectra were recorded on an IR
spectrophotometer using KBr discs and reported in wave
number (cm−1). MS (ESI) and HRMS (ESI) were recorded on a
Mass Spectrophotometer with a Q-ToF mass analyzer.
General procedure for the synthesis of 5,6-dihydro-1H-benzo-
[ f]naphtho[2,1-c]chromen-4(2H)-ylidene)acetonitrile 1a–f9
A mixture of the 4-morpholino-2-oxo-5,6-dihydro-2H-benzo[h]-
chromene-3-carbonitriles 9a–c (1.0 mmol), the respective 2-tet-
ralones 10 (1.2 mmol), and NaH (1.5 mmol) in THF was stirred
for 1–2.5 h at ambient temperature. The reaction was moni-
tored using TLC until completion. Excess THF was removed
under reduced pressure and the reaction mixture was poured
into ice-cool water with constant stirring followed by neutraliz-
ation with 10% HCl. The precipitate thus obtained was fil-
tered, washed with water, dried and purified with a neutral
alumina column using 20% CHCl3 in hexane as the eluent to
afford 1a–f.
(Z)-2-(11-Methoxy-5,6-dihydro-1H-benzo[f]naphtho[2,1-c]-
chromen-4(2H)-ylidene)acetonitrile (1b)
A
mixture of 4-morpholino-2-oxo-5,6-dihydro-2H-benzo[h]-
chromene-3-carbonitrile (9a, 308 mg, 1.0 mmol, 1 equiv.),
8-methoxy-2-tetralone (10, 211 mg, 1.2 mmol, 1.2 equiv.) and
NaH (60% dispersion in oil, 60 mg, 1.5 mmol, 1.5 equiv.) in
dry THF (5 ml) was stirred at room temperature for 1.5 h.
Using the general procedure described above, 208 mg (59%) of
1b was obtained as a yellow solid: Rf = 0.44 (CHCl3–n-hexane,
7 : 3, v/v); mp 146–148 °C (CHCl3–n-hexane); IR (KBr)
νmax/cm−1 = 2927 (m), 2847 (w), 2190 (s), 1628 (s); 1H NMR
Scheme 6 Synthesis of pyran-2-ylidenes 23 and α-pyrones 24.
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(300 MHz, CDCl3): δ = 2.42–3.11 (m, 11H), 4.43 (s, 1H), 6.54 1.387 g cm−3, μ (Mo-Kα) = 0.09 mm−1, F(000) = 1248, rectangu-
(d, J = 8.2 Hz, 1H), 6.84–6.98 (m, 4H), 7.08–7.17 (m, 2H) ppm; lar block, reddish, 17 307 reflections measured (Rint = 0.0861),
13C NMR (75.5 MHz, CDCl3): δ = 22.5, 27.2, 27.8, 29.0, 53.9, 3513 unique, wR2 = 0.2040 for all data, conventional R1
=
63.7, 108.8, 110.2, 118.8, 120.1, 121.3, 123.1, 123.4, 125.9, 0.0630 for 2408 Fo > 4σ(Fo) and 0.1060 for all 3513 data, S =
127.1, 127.6, 134.1, 135.6, 136.6, 137.6, 154.4, 159.2, 1.083 for all data and 209 parameters.
165.2 ppm; m/z (ESI): 354 [M + H+]; HRMS (ESI) calcd for
11-Methoxy-5,6-dihydro-4H-benzo[f]naphtho[2,1-c]chromen-
4-one (4b)
C24H19NO2 [M+ + 1] 354.1494, found 354.1491.
(Z)-2-(9-Methoxy-5,6-dihydro-1H-benzo[ f]naphtho[2,1-c]-
chromen-4(2H)-ylidene)acetonitrile (1e)
The (Z)-2-(11-methoxy-5,6-dihydro-1H-benzo[f]naphtho[2,1-c]-
chromen-4(2H)-ylidene)acetonitrile (1b, 353 mg, 1.0 mmol,
A mixture of 9-methoxy 4-morpholino-2-oxo-5,6-dihydro-2H- 1 equiv.) was treated with DDQ (908 mg, 4.0 mmol, 4 equiv.) in
benzo[h]chromene-3-carbonitrile (9e, 338 mg, 1.0 mmol, glacial acetic acid for 1 h. Using the general procedure
1 equiv.), 2-tetralone (10, 0.146 ml, 1.2 mmol, 1.2 equiv.) and described above, 157 mg (48%) of 4b was obtained as a light
NaH (60% dispersion in oil, 60 mg, 1.5 mmol, 1.5 equiv.) in yellow solid: Rf
= 0.47 (CHCl3–n-hexane, 7 : 3, v/v); mp
dry THF (5 ml) was stirred at room temperature for 1 h. Using 191–193 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 3020 (m),
the general procedure described above, 155 mg (44%) of 1e 2932 (w), 1725 (s), 1610 (m); 1H NMR (300 MHz, CDCl3) δ =
was obtained as a yellow solid: Rf = 0.47 (CHCl3–n-hexane, 7 : 3, 2.26–2.42 (m, 1H), 2.93–3.01 (m, 2H), 3.02 (s, 3H), 3.16–3.30
v/v); mp 162–164 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1
=
(m, 1H), 6.72 (d, J = 7.6 Hz, 1H), 6.84 (d, J = 7.6 Hz, 1H),
2932 (m), 2848 (w), 2199 (s), 1728 (w); 1H NMR (300 MHz, 6.94–7.03 (m, 1H), 7.17–7.51 (m, 5H), 7.88 (d, J = 8.8 Hz, 1H)
CDCl3): δ = 2.08–2.27 (m, 1H), 2.40–2.53 (m, 1H), 2.72–2.86 (m, ppm; 13C NMR (50.3 MHz, CDCl3) δ = 22.4, 27.9, 53.6, 107.6,
5H), 3.01–3.18 (m, 1H), 3.44 (s, 3H), 4.49 (s, 1H), 6.54 (d, J = 117.5, 120.5, 121.3, 123.5, 124.0, 126.0, 126.2, 127.6, 128.7,
1.7 Hz, 1H), 6.73–6.86 (m, 2H), 6.93–7.24 (m, 4H) ppm; 13C 131.3, 132.4, 136.1, 152.5, 155.1, 161.7 ppm; m/z (ESI): 329
NMR (75.5 MHz, CDCl3): δ = 23.0, 26.8, 27.3, 28.3, 55.1, 64.6, [M+ + H]; HRMS (ESI) calcd for C22H16O3 [M+ + 1] 329.1178,
110.8, 113.9, 115.2, 118.6, 125.6, 126.2, 126.3, 127.3, 127.6, found 329.1177.
128.3, 129.6, 131.4, 131.6, 134.1, 135.3, 157.3, 159.1,
14-Methoxy-5,6-dihydro-4H-benzo[f]naphtho[2,1-c]chromen-
164.8 ppm; m/z (ESI): 354 [M + H+]; HRMS (ESI) calcd for
4-one (4c)
C24H19NO2 [M+ + 1] 354.1494, found 354.1480.
The (Z)-2-(14-methoxy-5,6-dihydro-1H-benzo[f]naphtho[2,1-c]-
chromen-4(2H)-ylidene)acetonitrile (3c, 353 mg, 1.0 mmol,
General procedure for the synthesis of 4a–f
(Z)-2-(5,6-Dihydro-1H-benzo[f]naphtho[2,1-c]chromen-4(2H)- 1 equiv.) was treated with DDQ (908 mg, 4.0 mmol, 4 equiv.) in
ylidene)acetonitriles (1a–f) were treated with 4.0 mmol of DDQ glacial acetic acid for 1 h. Using the general procedure
in AcOH at room temp. for 1 h. After completion, the reaction described above, 170 mg (52%) of 4c was obtained as a light
mixture was filtered and the filtrate was collected and evapor- yellow solid: Rf
= 0.50 (CHCl3–n-hexane, 7 : 3, v/v); mp
ated to dryness. Thereafter, the crude obtained was purified 149–151 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 2942 (m),
through neutral alumina using 60% CHCl3 in hexane as eluent 2841 (w), 1711 (s); 1H NMR (300 MHz, CDCl3) δ = 2.23–2.42 (m,
to afford 4a–f.
1H), 2.91–3.02 (m, 2H), 3.17–3.30 (m, 1H), 4.03 (s, 3H), 6.79 (d,
J = 7.7 Hz, 1H), 7.06–7.51 (m, 7H), 8.45 (d, J = 9.1 Hz, 1H) ppm;
13C NMR (75.5 MHz, CDCl3) δ = 22.7, 28.0, 55.7, 103.6, 112.1,
5,6-Dihydro-4H-benzo[f]naphtho[2,1-c]chromen-4-one (4a)
The
(Z)-2-(5,6-dihydro-1H-benzo[f]naphtho[2,1-c]chromen-4 116.2, 119.9, 123.0, 125.7, 125.9, 126.1, 126.6, 127.8, 129.0,
(2H)-ylidene)acetonitrile (1a, 323 mg, 1.0 mmol, 1 equiv.) was 129.9, 130.2, 132.5, 138.4, 146.2, 152.9, 155.6, 161.6 ppm; m/z
treated with DDQ (908 mg, 4.0 mmol, 4 equiv.) in glacial acetic (ESI): 329 [M+ + H]; HRMS (ESI) calcd for C22H16O3 [M+ + 1]
acid for 1 h. Using the general procedure described above, 329.1178, found 329.1180.
172 mg (58%) of 4a was obtained as a light yellow solid: Rf =
12-Methoxy-5,6-dihydro-4H-benzo[f]naphtho[2,1-c]chromen-
0.57 (CHCl3–n-hexane, 7 : 3, v/v); mp 204–206 °C (CHCl3–n-
4-one (4d)
hexane); IR (KBr) νmax/cm−1 = 2931 (w), 2744 (w), 1704 (s), 1609
(m); 1H NMR (300 MHz, CDCl3) δ = 2.23–2.41 (m, 1H), The (Z)-2-(12-methoxy-5,6-dihydro-1H-benzo[f]naphtho[2,1-c]-
2.90–3.00 (m, 2H), 3.16–3.29 (m, 1H), 7.05–7.15 (m, 1H), chromen-4(2H)-ylidene)acetonitrile (1d, 353 mg, 1.0 mmol,
7.20–7.30 (m, 2H), 7.31–7.53 (m, 4H), 7.81–7.96 (m, 3H) ppm; 1 equiv.) was treated with DDQ (908 mg, 4.0 mmol, 4 equiv.) in
13C NMR (75.5 MHz, CDCl3) δ = 22.8, 28.1, 112.4, 117.3, 125.4, glacial acetic acid for 1 h. Using the general procedure
125.5, 125.8, 126.7, 127.2, 127.9, 128.6, 128.9, 129.0, 130.0, described above, 181 mg (55%) of 4d was obtained as a light
131.1, 132.0, 132.4, 138.5, 145.9, 152.6, 161.5 ppm; m/z yellow solid: Rf
(ESI): 299 [M+ + H]; HRMS (ESI) calcd for C21H14O2 [M+ + 1] 176–178 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 3022 (m),
299.1072, found 299.1081.
1629 (m); 1H NMR (300 MHz, CDCl3) δ = 2.16–2.33 (m, 1H),
= 0.52 (CHCl3–n-hexane, 7 : 3, v/v); mp
The crystal data of 4a (CCDC deposit no: 877580): 2.84–3.14 (m, 2H), 3.12 (s, 1H), 3.37 (s, 3H), 6.96–7.04 (m, 1H),
C21H14O2, M = 298.32, Orthorhombic, Pbca, a = 15.050(5) Å, 7.05–7.39 (m, 6H), 7.67 (d, J = 8.9 Hz, 1H), 7.78 (d, J = 8.8 Hz,
b = 8.960(3) Å, c = 21.187(7) Å, V = 2857(2) Å3, Z = 8, Dc
=
1H) ppm; 13C NMR (75.5 MHz, CDCl3) δ = 22.6, 28.1, 54.7,
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107.4, 111.5, 114.7, 117.6, 125.6, 126.3, 126.4, 128.0, 129.3, 7.04–7.09 (m, 2H), 7.20–7.51 (m, 5H), 7.66 (d, J = 8.6 Hz, 1H),
129.9, 130.0, 130.3, 131.7, 132.1, 138.7, 145.9, 153.2, 157.1, 7.80–7.94 (m, 2H); 13C NMR (75.5 MHz, CDCl3): δ = 24.0, 27.8,
161.5 ppm; m/z (ESI): 329 [M+ + H]; HRMS (ESI) calcd for 113.5, 116.4, 118.2, 125.3, 125.7, 126.0, 127.0, 127.4, 127.9,
C22H16O3 [M+ + 1] 329.1178, found 329.1176.
128.4, 128.6, 129.5, 131.2, 131.8, 132.5, 137.1, 137.3, 151.8,
158.1 ppm; m/z (ESI): 356 [M+ + H]; HRMS (ESI) calcd for
C23H14ClNO [M+ + 1] 356.0842, found 356.0850.
9-Methoxy-5,6-dihydro-4H-benzo[f]naphtho[2,1-c]chromen-
4-one (4e)
General procedure for the synthesis of 8a–c17
The
(Z)-2-(9-methoxy-5,6-dihydro-1H-benzo[f]naphtho[2,1-c]-
chromen-4(2H)-ylidene)acetonitrile (1e, 353 mg, 1.0 mmol, A mixture of methyl 2-cyano-3,3-dimethylthioacrylate 7 (10.1 g,
1 equiv.) was treated with DDQ (908 mg, 4.0 mmol, 4 equiv.) in 0.05 mol), the respective 1-tetralone 6a–c (7.3 ml, 0.05 mol)
glacial acetic acid for 1 h. Using the general procedure was stirred in the presence of powdered KOH (3.3 g, 0.06 mol)
described above, 187 mg (57%) of 4e was obtained as a light in DMSO (50 ml) for 5–6
h at ambient temperature.
yellow solid: Rf 0.45 (CHCl3–n-hexane, 7 : 3, v/v); mp Completion of the reaction was monitored using TLC and on
=
163–165 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 2930 (m), completion the reaction mixture was poured into ice-cool
2851 (w), 1708 (s); 1H NMR (300 MHz, CDCl3) δ = 2.23–2.42 (m, water with constant stirring and the resulting precipitate was
1H), 2.87–2.95 (m, 2H), 3.16–3.29 (m, 1H), 3.52 (s, 3H), 6.81 (d, filtered, washed with water, dried, and purified through a
J = 2.4 Hz, 1H), 6.92 (dd, J = 8.2, 2.6 Hz, 1H), 7.27–7.36 (m, silica gel column using 2% MeOH in CHCl3 as the eluent to
2H), 7.40–7.55 (m, 2H), 7.83–7.99 (m, 3H) ppm; 13C NMR afford 8a–c.
(75.5 MHz, CDCl3) δ = 22.7, 27.1, 55.3, 112.2, 114.1, 114.2,
116.3, 117.3, 125.4, 125.4, 127.0, 127.4, 128.6, 128.7, 128.8,
Synthesis of 9-methoxy-4-(methylthio)-2-oxo-5,6-dihydro-2H-
benzo[h]chromene-3-carbonitrile (8c)
130.6, 131.2, 132.0, 133.1, 139.2, 145.8, 152.5, 157.5,
161.4 ppm; m/z (ESI): 329 [M+ + H]; HRMS (ESI) calcd for A mixture of methyl 2-cyano-3,3-dimethylthioacrylate 7 (10.1 g,
C22H16O3 [M+ + 1] 329.1178, found 329.1175.
0.05 mol) and 7-methoxy-1-tetralone 6c (8.8 g, 0.05 mol) was
stirred in the presence of powdered KOH (3.3 g, 0.06 mol) in
DMSO (50 ml) for 6 h. Using the general procedure described
above, 13 g (87%) of 8c was obtained as a yellow solid: Rf =
8-Methoxy-5,6-dihydro-4H-benzo[f]naphtho[2,1-c]chromen-
4-one (4f)
The
(Z)-2-(9-methoxy-5,6-dihydro-1H-benzo[f]naphtho[2,1-c]- 0.56 (MeOH–CHCl3, 1 : 25 v/v); mp 188–190 °C (CHCl3–
chromen-4(2H)-ylidene)acetonitrile (1f, 353 mg, 1.0 mmol, n-hexane); IR (KBr) νmax/cm−1 = 3339 (m), 2212 (w), 1713 (m);
1 equiv.) was treated with DDQ (908 mg, 4.0 mmol, 4 equiv.) in 1H NMR (300 MHz, CDCl3): δ = 2.74–2.83 (m, 2H), 2.84–2.93
glacial acetic acid for 1 h. Using the general procedure (m, 2H), 2.99 (s, 3H), 3.84 (s, 3H), 6.92–7.02 (m, 1H), 7.14 (d,
described above, 154 mg (47%) of 4f was obtained as a light J = 8.4 Hz, 1H), 7.34–7.41 (m, 1H) ppm; 13C NMR (50.3 MHz,
yellow solid: Rf
= 0.44 (CHCl3–n-hexane, 7 : 3, v/v); mp CDCl3): δ = 17.6, 22.0, 26.1, 55.7, 108.6, 119.3, 129.0, 130.6,
156–158 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 2942 (m), 131.0, 138.4, 159.1 ppm; m/z (ESI): 300 [M+ + H]; HRMS (ESI)
2842 (w), 1653 (m); 1H NMR (300 MHz, CDCl3) δ = 2.25–2.44 calcd for C16H13NO3S [M+ + 1] 300.0694, found 300.0695.
(m, 1H), 2.86–3.07 (m, 2H), 3.17–3.28 (m, 1H), 3.87 (s, 3H),
General procedure for the synthesis of 9a–c17
6.61–6.69 (m, 1H), 6.91 (s, 1H), 7.17–7.32 (m, 2H), 7.39–7.53
(m, 2H), 7.82–7.99 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3) A mixture of 8 (2.7 g, 0.01 mol) and morpholine (1.3 ml,
δ = 22.5, 28.5, 55.4, 111.3, 112.4, 113.2, 117.3, 124.5, 125.2, 0.012 mol) in methanol (25 ml) was refluxed for 5 h. The reac-
125.3, 125.4, 127.1, 128.5, 129.1, 130.6, 131.1, 131.9, 140.7, tion mixture was cooled to room temperature, and the precipi-
145.9, 152.5, 160.9, 161.6 ppm; m/z (ESI): 329 [M+ + H]; HRMS tate obtained was filtered, washed with methanol, dried, and
(ESI) calcd for C22H16O3 [M+ + 1] 329.1178, found 329.1207.
crystallized from methanol to afford 9a–c.
2-Chloro-2-(5,6-dihydro-4H-benzo[f]naphtho[2,1-c]chromen-
4-ylidene)acetonitrile (5a)
Synthesis of 9-methoxy-4-morpholino-2-oxo-5,6-dihydro-2H-
benzo[h]chromene-3-carbonitrile (9c)
The
(Z)-2-(5,6-dihydro-1H-benzo[f]naphtho[2,1-c]chromen-4- A mixture of 8c (3.0 g, 0.01 mol) and morpholine (1.3 ml,
(2H)-ylidene)acetonitrile (1a, 323 mg, 1.0 mmol, 1 equiv.) was 0.012 mol) in methanol (25 ml) was refluxed for 5 h. The reac-
treated with DDQ (908 mg, 4.0 mmol, 4 equiv.) in dioxane for tion mixture was cooled to room temperature, and the precipi-
4 h at reflux temperature. After completion, reaction mixture tate obtained was filtered, washed with methanol, dried,
was filtered and filtrate was collected and evaporated to and crystallized from methanol to afford 3.01 g (89%) of 9c as
dryness. Thereafter, the crude mixture was purified through a yellow solid: Rf = 0.49 (MeOH–CHCl3, 1 : 25 v/v); mp
neutral alumina using 10% CHCl3 in hexane as the eluent to 174–176 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 3021 (w),
1
afford 43 mg (12%) of 5a {along with 128 mg (43%) of 4a}as a 2215 (w), 1635 (m); H NMR (300 MHz, CDCl3): δ = 2.56–2.72
light yellow solid: Rf = 0.71 (CHCl3–n-hexane, 7 : 3 v/v); mp (m, 2H), 2.75–2.91 (m, 2H), 3.52–3.69 (m, 4H), 3.82 (s, 3H),
178–180 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 2924 (s), 3.85–3.98 (m, 4H), 6.87–7.01 (m, 1H), 7.13 (d, J = 8.3 Hz, 1H),
2855 (m), 2193 (s), 1540 (s); 1H NMR (300 MHz, CDCl3): δ = 7.28–7.39 (m, 1H) ppm; 13C NMR (50.3 MHz, CDCl3): δ = 23.8,
2.32–2.55 (m, 1H), 2.92–3.03 (m, 2H), 3.65–3.76 (m, 1H), 26.9, 51.7, 55.7, 67.1, 81.5, 108.7, 116.5, 118.7, 128.5, 129.9,
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157.7, 159.1, 166.6 ppm; m/z (ESI): 339 [M+ + H]; HRMS (ESI) 122.3, 124.5, 141.0, 144.6, 155.2 ppm; m/z (ESI): 267 [M+ + H];
calcd for C19H18N2O4 [M+ + 1] 339.1345, found 339.1336.
HRMS (ESI) calcd for C10H3Cl2N3O2 [M+ + 1] 267.9681, found
267.9641.
General procedure for the synthesis of 11a,b
The crystal data for 12 (CCDC deposit no: 877581):
5,6-Dihydro-4H-benzo[f]naphtho[2,1-c]chromen-4-ones (4a,b) C12H6Cl2N4O2, M = 309.11, monoclinic, C2/c, a = 20.542(2) Å,
were treated with 15 mmol of DDQ in benzene and refluxed b = 7.512(1) Å, c = 18.182(2) Å, β = 109.593(1)°, V = 2643.2(5) Å3,
for 24 h. After completion, reaction mixture was filtered and Z = 8, Dc = 1.554 g cm−3, μ (Mo-Kα) = 0.50 mm−1, F(000) =
filtrate was collected and evaporated to dryness. Thereafter, 1248, rectangular block, yellow, 8334 reflections measured
the crude obtained was purified through neutral alumina (Rint = 0.0537), 4295 unique, wR2 = 0.1660 for all data, conven-
using 40% CHCl3 in hexane as the eluent.
tional R1 = 0.0594 for 2448 Fo > 4σ(Fo) and 0.1133 for all 4295
data, S = 0.993 for all data and 183 parameters.
4H-Benzo[f]naphtho[2,1-c]chromen-4-one (11a)
General procedure for the synthesis of 15a–f
The 5,6-dihydro-4H-benzo[f]naphtho[2,1-c]chromen-4-one (4a,
298 mg, 1.0 mmol, 1 equiv.) was treated with DDQ (3405 mg, A mixture of the methyl 4-(methylthio)-2-oxo-6-aryl-2H-pyran-
15.0 mmol, 15 equiv.) in refluxing benzene for 24 h. Using the 3-carboxylates 14 (1.0 mmol), the respective resorcinol 13
general procedure described above, 177 mg (60%) of 11a was (2.0 mmol) and NaH (60% dispersion in oil, 200 mg,
obtained as an off-white solid: Rf = 0.71 (CHCl3–n-hexane, 7 : 3, 5.0 mmol, 5 equiv.) in dry DMF (5 ml) was stirred at a temp-
v/v); mp 237–239 °C {lit.18 236–238 °C} (CHCl3–n-hexane); IR erature of 60 °C for 3–4 h. Completion of the reaction was
(KBr) νmax/cm−1 = 2924 (m), 2855 (w), 1730 (s); 1H NMR monitored using TLC and on completion the reaction mixture
(300 MHz, CDCl3) δ = 7.32–7.55 (m, 3H), 7.57–7.73 (m, 2H), was poured into crushed ice with vigorous stirring and finally
7.88–8.16 (m, 6H), 8.37 (d, J = 8.5 Hz, 1H) ppm; 13C NMR neutralized with 10% HCl. The precipitate obtained was fil-
(75.5 MHz, CDCl3) δ = 112.9, 117.2, 121.6, 124.2, 125.4, 125.5, tered and purified on a silica gel column using 10% ethyl
125.8, 127.2, 128.3, 128.4, 129.1, 129.4, 129.8, 131.2, 131.7, acetate in n-hexane as the eluent to afford 15a–f as a mixture
134.9, 136.7, 150.5, 161.8 ppm; m/z (ESI): 297 [M+ + H]; HRMS of cis- and trans-isomers.
(ESI) calcd for C21H12O2 [M+ + 1] 297.0916, found 297.0900.
(Z/E)-Methyl 2-(7-hydroxy-4-phenyl-2H-chromen-2-ylidene)-
11-Methoxy-4H-benzo[f]naphtho[2,1-c]chromen-4-one (11b)
acetate (15a)
The 11-methoxy-5,6-dihydro-4H-benzo[f]naphtho[2,1-c]- A mixture of methyl 4-(methylthio)-2-oxo-6-phenyl-2H-pyran-
chromen-4-one (4b, 328 mg, 1.0 mmol, 1 equiv.) was treated 3-carboxylate (14a, 276 mg, 1.0 mmol, 1 equiv.), resorcinol
with DDQ (3405 mg, 15.0 mmol, 15 equiv.) in refluxing (13a, 220 mg, 2.0 mmol, 2 equiv.) and NaH (60% dispersion in
benzene for 24 h. Using the general procedure described oil, 200 mg, 5.0 mmol, 5 equiv.) in dry DMF (5 ml) was stirred
above, 185 mg (57%) of 11b was obtained as an off-white solid: at a temperature of 60 °C for 3 h. Using the general procedure
Rf = 0.60 (CHCl3–n-hexane, 7 : 3, v/v); mp 214–216 °C (CHCl3–n- described above, 200 mg (68%) of 15a was obtained as a
hexane); IR (KBr) νmax/cm−1 = 2946 (m), 2835 (m), 1654 (m); 1H mixture of cis- and trans-isomers, as a yellow solid: Rf = 0.47
NMR (200 MHz, CDCl3) δ = 2.98 (s, 3H), 6.81 (d, J = 7.4 Hz, (ethyl acetate–n-hexane, 1 : 9, v/v); mp 210–212 °C (ethyl
1H), 7.28–7.38 (m, 1H), 7.52–7.64 (m, 4H), 7.79 (d, J = 8.5 Hz, acetate–n-hexane); IR (KBr) νmax/cm−1 = 3584 (s), 1636 (w);
1H), 7.91–8.02 (m, 3H), 8.30 (d, J = 8.6 Hz, 1H) ppm; 13C NMR 1H NMR (300 MHz, CDCl3 + DMSO-d6): δ = 4.43 (s, 3H, cis),
(75.5 MHz, CDCl3) δ = 53.9, 106.6, 110.7, 117.5, 120.7, 123.3, 4.47 (s, 3H, trans), 5.72 (s, 1H, trans), 6.09 (s, 1H, cis), 6.83 (s,
125.3, 126.0, 126.3, 128.0, 128.2, 128.7, 131.3, 134.7, 1H, trans), 7.31–7.38 (m, 2H, cis + trans), 7.42 (d, J = 2.2 Hz,
155.6 ppm; m/z (ESI): 327 [M+ + H]; HRMS (ESI) calcd for 1H, cis), 7.61 (d, J = 2.2 Hz, 1H, trans), 7.82–7.92 (m, 2H, cis +
C22H14O3 [M+ + 1] 327.1021, found 327.1016.
trans), 8.10–8.21 (m, 12H, cis + trans), 10.37 (s, 1H, trans),
10.38 (s, 1H, cis) ppm; 13C NMR (75.5 MHz, DMSO-d6): δ =
50.0, 89.8, 102.0, 111.2, 111.7, 112.6, 126.7, 127.8, 128.4, 128.6,
135.7, 143.8, 153.3, 160.3, 162.1, 166.5; m/z (ESI): 295 [M + H+];
3-Amino-6,7-dichloro-5-hydroxybenzofuran-2,4-
dicarbonitrile (12)
The (Z)-2-(5,6-dihydro-4H-benzo[ f]naphtho[2,1-c]chromen-4- HRMS (ESI) calcd for C18H14O4 [M+ + 1] 295.0970; found
ylidene)acetonitrile (2a, 321 mg, 1.0 mmol, 1 equiv.) was 295.0965.
treated with DDQ (554 mg, 2.0 mmol, 2 equiv.) in glacial acetic
acid for 4 h. After completion, the reaction mixture was filtered
and filtrate was collected and evaporated to dryness. There-
(Z/E)-Methyl 2-(7-hydroxy-4-(naphthalen-2-yl)-2H-chromen-
2-ylidene)acetate (15b)
after, the crude obtained was purified with a neutral alumina A mixture of methyl 4-(methylthio)-6-(naphthalen-2-yl)-2-oxo-
column using 10% MeOH in chloroform as the eluent 2H-pyran-3-carboxylate (14b, 326 mg, 1.0 mmol, 1 equiv.),
to afford 88 mg (33%) 12 (along with 4a) as an off-white solid: resorcinol (13a, 220 mg, 2.0 mmol, 2 equiv.) and NaH (60%
Rf = 0.31 (MeOH–CHCl3, 1 : 4, v/v); mp > 250 °C (CH3CN); IR dispersion in oil, 200 mg, 5.0 mmol, 5 equiv.) in dry DMF
(KBr) νmax/cm−1 = 3489 (w), 3374 (m), 3151 (m), 2222 (s); 1H (5 ml) was stirred at a temperature of 60 °C for 4 h. Using the
NMR (300 MHz, DMSO-d6) δ = 6.12 (brs, 2H) ppm; 13C NMR general procedure described above, 227 mg (66%) of 15b was
(100.6 MHz, DMSO-d6) δ = 90.8, 111.7, 112.9, 114.3, 119.7, obtained as a mixture of cis- and trans-isomers, as a yellow
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solid: Rf
224–226 °C (ethyl acetate–n-hexane); IR (KBr) νmax/cm−1 = 3201 (w), chromen-2-ylidene)acetate (15e)
2857 (m), 1647 (m), 1562 (w); 1H NMR (300 MHz, CDCl3
= 0.56 (ethyl acetate–n-hexane, 1 : 9, v/v); mp (Z/E)-Methyl 2-(4-(4-chlorophenyl)-7-hydroxy-8-methyl-2H-
+
A mixture of methyl 6-(4-chlorophenyl)-4-(methylthio)-2-oxo-
2H-pyran-3-carboxylate (14d, 310 mg, 1.0 mmol, 1 equiv.),
2-methyl-resorcinol (13c, 248 mg, 2.0 mmol, 2 equiv.) and NaH
(60% dispersion in oil, 200 mg, 5.0 mmol, 5 equiv.) in dry
DMF (5 ml) was stirred at a temperature of 60 °C for 3 h. Using
the general procedure described above, 205 mg (60%) of 15e
was obtained as a mixture of cis- and trans-isomers, as a yellow
DMSO-d6): δ = 4.09 (s, 3H, cis), 4.13 (s, 3H, trans), 5.42 (s, 1H,
trans), 5.77 (s, 1H, cis), 6.62 (s, 1H, trans), 6.98–7.05 (m, 2H, cis +
trans), 7.10 (d, J = 1.74 Hz, 1H, trans), 7.27 (s, 1H, trans), 7.54–7.63
(m, 2H, cis + trans), 7.91–7.99 (m, 8H, cis + trans), 8.31–8.38 (m,
8H, cis + trans), 10.22 (s, 1H, trans), 10.22 (s, 1H, cis) ppm; 13C
NMR (75.5 MHz, DMSO-d6): δ = 50.9, 90.9, 102.9, 112.3, 112.7,
113.9, 126.4, 127.2, 127.4, 127.8, 127.9, 128.0, 128.7, 128.8, 133.3,
133.4, 134.2, 144.7, 154.3, 161.3, 163.0, 167.5; m/z (ESI): 345 [M +
H+]; HRMS(ESI) calcd for C22H16O4 [M+ + 1] 345.1126, found
345.1188.
solid: Rf
= 0.56 (ethyl acetate–n-hexane, 1 : 9, v/v); mp
226–228 °C (ethyl acetate–n-hexane); IR (KBr) νmax/cm−1 = 3458
1
(w), 1728 (s), 1670 (s), 1586 (s); H NMR (300 MHz, DMSO-d6):
δ = 2.14 (s, 3H, cis), 2.26 (s, 3H, trans), 3.59 (s, 3H, cis), 3.62 (s,
3H, trans), 5.14 (s, 1H, trans), 5.37 (s, 1H, cis), 6.40 (s, 1H,
trans), 6.69 (d, J = 8.2 Hz, 2H, cis + trans), 6.92 (d, J = 8.4 Hz,
2H, cis + trans), 7.45–7.63 (m, 10H, cis + trans), 10.25 (s, 1H,
trans), 10.35 (s, 1H, cis) ppm; 13C NMR (75.5 MHz, DMSO-d6):
δ = 7.9, 50.4, 90.4, 111.0, 111.4, 112.8, 123.8, 128.8, 130.2,
133.8, 135.2, 143.5, 151.5, 158.7, 162.5, 167.0; HRMS (ESI)
calcd for C19H15ClO4 [M+ + 1] 343.0737, found 343.0729.
(Z/E)-Methyl 2-(4-(4-bromophenyl)-7-hydroxy-2H-chromen-
2-ylidene)acetate (15c)
A mixture of methyl 6-(4-bromophenyl)-4-(methylthio)-2-oxo-
2H-pyran-3-carboxylate (14c, 354 mg, 1.0 mmol, 1 equiv.),
resorcinol (13a, 220 mg, 2.0 mmol, 2 equiv.) and NaH (60%
dispersion in oil, 200 mg, 5.0 mmol, 5 equiv.) in dry DMF
(5 ml) was stirred at a temperature of 60 °C for 4 h. Using the
general procedure described above, 257 mg (69%) of 15c was
obtained as a mixture of cis- and trans-isomers, as a yellow
(Z/E)-Methyl 2-(7-hydroxy-4-(thiophen-2-yl)-2H-chromen-2-
ylidene)acetate (15f)
A mixture of methyl 4-(methylthio)-2-oxo-6-(thiophen-2-yl)-2H-
pyran-3-carboxylate (14e, 282 mg, 1.0 mmol, 1 equiv.), resorci-
nol (13a, 220 mg, 2.0 mmol, 2 equiv.) and NaH (60% dis-
persion in oil, 200 mg, 5.0 mmol, 5 equiv.) in dry DMF (15 ml)
was stirred at a temperature of 60 °C for 4 h. Using the general
procedure described above, 186 mg (62%) of 15f was obtained
as a mixture of cis- and trans-isomers, as a yellow solid: Rf =
0.58 (ethyl acetate–n-hexane, 1 : 9, v/v); mp 234–236 °C (ethyl
solid: Rf
= 0.56 (ethyl acetate–n-hexane, 1 : 9, v/v); mp
284–252 °C (ethyl acetate–n-hexane); IR (KBr) νmax/cm−1 = 3201
1
(w), 2857 (m), 1647 (m), 1562 (w); H NMR (300 MHz, DMSO-
d6+CDCl3): δ = 3.59 (s, 1H, cis), 3.60 (s, 1H, trans), 5.15 (s, 1H,
trans), 5.32 (s, 1H, cis), 6.41 (s, 1H, trans), 6.60–6.65 (m, 2H, cis
+ trans), 7.05–7.10 (m, 1H, cis + trans), 7.37–7.46 (m, 2H, cis +
trans), 7.51 (s, 1H, cis), 7.70–7.75 (m, 2H, cis + trans), 10.44 (s,
1H, OH, D2O exchange); 13C NMR (75 MHz, DMSO-d6): δ =
50.9, 79.6, 91.2, 102.9, 111.8, 112.7, 113.7, 123.0, 127.5, 130.1,
132.3, 135.9, 143.5, 154.2, 161.4, 162.8, 167.4; HRMS (ESI)
calcd for C18H13BrO4 [M+ + 1] 373.0075, found 373.0066.
1
acetate–n-hexane); IR (KBr) νmax/cm−1 = 3600 (s), 1650 (m); H
NMR (300 MHz, DMSO-d6): δ = 3.62 (s, 3H, cis + trans), 5.20 (s,
1H, trans), 5.31 (s, 1H, cis), 6.57 (s, 1H, trans), 6.63–6.75 (m,
2H, cis + trans), 7.24–7.31 (m, 1H, cis + trans), 7.44–7.62 (m,
2H, cis + trans), 7.70–7.83 (m, 2H, cis + trans), 10.50 (s, 1H, OH,
D2O exchange); 13C NMR (75.5 MHz, DMSO-d6): δ = 51.0, 91.2,
103.1, 111.3, 112.8, 113.7, 127.5, 128.6, 128.8, 128.8, 129.4,
137.1, 137.5, 154.3, 161.5, 162.5, 167.4; HRMS (ESI) calcd for
C16H12O4S [M+ + 1] 301.0535, found 301.0528.
(Z/E)-Methyl 2-(6-chloro-7-hydroxy-4-phenyl-2H-chromen-
2-ylidene)acetate (15d)
A mixture of methyl 4-(methylthio)-2-oxo-6-phenyl-2H-pyran-3-
carboxylate (14a, 276 mg, 1.0 mmol, 1 equiv.), 4-chloro-resorci-
nol (13b, 286 mg, 2.0 mmol, 2 equiv.) and NaH (60% dis-
persion in oil, 200 mg, 5.0 mmol, 5 equiv.) in dry DMF (15 ml)
was stirred at a temperature of 60 °C for 3 h. Using the general
procedure described above, 230 mg (70%) of 15d was obtained
as a mixture of cis- and trans-isomers, as a yellow solid: Rf =
0.58 (ethyl acetate–n-hexane, 1 : 9, v/v); mp 234–236 °C (ethyl
General procedure for the synthesis of 16a–f
(Z/E)-Methyl 2-(7-hydroxy-2H-chromen-2-ylidene)-acetates (15a–f)
were treated with 2.0 mmol of DDQ in dioxane at 80 °C
for 1–2 h. After completion, the reaction mixture was filtered
and the filtrate was collected and evaporated to dryness. There-
after, the crude obtained was purified through neutral
alumina using 10% acetone–n-hexane as the eluent to afford
16a–f.
acetate–n-hexane); IR (KBr) νmax/cm−1 = 3600 (s), 1650 (m); H
1
NMR (300 MHz, DMSO-d6): δ = 3.59 (s, 3H, cis), 3.60 (s, 3H,
trans), 5.20 (s, 1H, trans), 5.36 (s, 1H, cis), 6.49 (s, 1H, trans),
6.84 (s, 2H, cis + trans), 7.09 (s, 1H, trans), 7.11 (s, 1H, cis),
7.42–7.57 (m, 12H, cis + trans), 11.30 (brs, 2H, cis + trans) ppm;
7-Hydroxy-4-phenyl-2H-chromen-2-one (16a)
13C NMR (75.5 MHz, DMSO-d6): δ = 51.1, 91.9, 104.1, 113.2, The methyl 2-(7-hydroxy-4-phenyl-2H-chromen-2-ylidene)-
114.6, 116.4, 126.7, 128.7, 129.4, 129.6, 129.8, 129.5, 136.0, acetate (15a, 147 mg, 0.5 mmol, 1 equiv.) was treated with
143.4, 152.5, 156.4, 162.4, 167.3; HRMS (ESI) calcd for DDQ (227 mg, 1.0 mmol, 2 equiv.) in dioxane (5 ml) at 80 °C
C18H13ClO4 [M+ + 1] 329.0581, found 329.0574.
for 2 h. Using the general procedure described above, 66 mg
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(54%) of 16a was obtained as a yellow solid: Rf = 0.56 (acetone– 4-(4-Chlorophenyl)-7-hydroxy-8-methyl-2H-chromen-2-one
n-hexane, 1 : 10, v/v); mp 234–236 °C {lit.15 210–211 °C} (16e)
(acetone–n-hexane); IR (KBr) νmax/cm−1 = 3102 (m), 1695 (s),
The methyl 2-(4-(4-chlorophenyl)-7-hydroxy-8-methyl-2H-
1595 (s); 1H NMR (300 MHz, CDCl3 + DMSO-d6) δ = 6.03 (s,
chromen-2-ylidene)acetate (15e, 171 mg, 0.5 mmol, 1 equiv.)
1H), 6.65–6.79 (m, 2H), 7.24 (d, J = 13.0 Hz, 1H), 7.36–7.52 (m,
was treated with DDQ (227 mg, 1.0 mmol, 2 equiv.) in dioxane
(5 ml) at 80 °C for 1 h. Using the general procedure described
above, 60 mg (42%) of 16e was obtained as a yellow solid: Rf =
5H), 10.27 (s, 1H); 13C NMR (75.5 MHz, CDCl3 + DMSO-d6) δ =
102.6, 110.0, 110.7, 112.9, 127.7, 127.9, 128.4, 129.1, 135.1,
155.5, 155.6, 160.5, 161.3; HRMS (ESI) calcd for C15H10O3
0.48 (acetone–n-hexane, 1 : 10, v/v); mp 248–250 °C (acetone–n-
[M+ + 1] 239.0708, found: 239.0706.
hexane); IR (KBr) νmax/cm−1 = 3398 (w), 1682 (s); 1H NMR
(300 MHz, DMSO-d6) δ = 2.20 (s, 3H), 6.16 (s, 1H), 6.84 (d, J =
8.6 Hz, 1H), 7.09 (d, J = 8.4 Hz, 1H), 7.48–7.64 (m, 4H), 10.58
7-Hydroxy-4-(naphthalen-2-yl)-2H-chromen-2-one (16b)
The methyl 2-(7-hydroxy-4-(naphthalen-2-yl)-2H-chromen- (s, 1H); 13C NMR (75.5 MHz, DMSO-d6) δ = 8.0, 110.0, 110.5,
2-ylidene)acetate (15b, 172 mg, 0.5 mmol, 1 equiv.) was treated 111.4, 112.0, 124.7, 128.8, 130.3, 134.0, 134.3, 153.3, 154.8,
with DDQ (227 mg, 1.0 mmol, 2 equiv.) in dioxane (5 ml) at 159.2, 160.4; HRMS (ESI) calcd for C16H11ClO3 [M+ + 1]
80 °C for 2 h. Using the general procedure described above, 287.0475; found: 287.0477.
80 mg (55%) of 16b was obtained as a yellow solid: Rf = 0.48
7-Hydroxy-4-(thiophen-2-yl)-2H-chromen-2-one (16f)
(acetone–n-hexane, 1 : 10, v/v); mp 214–216 °C (acetone–n-
hexane); IR (KBr) νmax/cm−1 = 3402 (m), 1629 (s); 1H NMR
(300 MHz, CDCl3 + DMSO-d6) δ = 6.20 (s, 1H), 6.75 (dd, J = 8.6,
2.2 Hz, 1H), 6.86 (d, J = 2.2 Hz, 1H), 7.34 (d, J = 8.7 Hz, 1H),
7.51–7.62 (m, 3H), 7.94–8.03 (m, 4H), 10.18 (s, 1H); 13C NMR
(75 MHz, CDCl3 + DMSO-d6) δ = 102.7, 110.3, 110.9, 112.9,
125.2, 126.4, 126.7, 127.3, 127.4, 127.7, 127.8, 128.0, 132.4,
132.7, 132.9, 155.5, 155.6, 160.7, 161.2; HRMS (ESI) calcd for
C19H12O3 [M+ + 1] 289.0865, found: 289.0859.
The methyl 2-(7-hydroxy-4-(thiophen-2-yl)-2H-chromen-2-
ylidene)acetate (15f, 150 mg, 0.5 mmol, 1 equiv.) was treated
with DDQ (227 mg, 1.0 mmol, 2 equiv.) in refluxing dioxane
(5 ml) at 90 °C for 2 h. Using the general procedure described
above, 110 mg (45%) of 16f was obtained as a yellow solid: Rf =
0.63 (acetone–n-hexane, 1 : 10, v/v); mp 236–238 °C (acetone–n-
hexane); IR (KBr) νmax/cm−1 = 3413 (s), 1730 (w); 1H NMR
(300 MHz, CDCl3 + DMSO-d6) δ = 6.27 (s, 1H), 6.87 (d, J =
7.2 Hz, 2H), 7.28–7.35 (m, 1H), 7.53 (d, J = 2.3 Hz, 1H),
7.69–7.74 (m, 1H), 7.81 (d, J = 9.3 Hz, 1H), 7.98 (s, 1H), 10.40
(s, 1H, OH, D2O exchange); 13C NMR (CDCl3 + DMSO-d6) δ =
103.2, 110.3, 113.4, 127.8, 128.2, 128.7, 129.4, 136.2, 148.2,
155.9, 160.5, 161.9; HRMS (ESI) calcd for C13H8O3S [M+ + 1]
245.0272; found: 245.0266.
4-(4-Bromophenyl)-7-hydroxy-2H-chromen-2-one (16c)
The methyl 2-(4-(4-bromophenyl)-7-hydroxy-2H-chromen-2-
ylidene)acetate (15c, 185 mg, 0.5 mmol, 1 equiv.) was treated
with DDQ (227 mg, 1.0 mmol, 2 equiv.) in refluxing dioxane
(5 ml) at 90 °C for 1 h. Using the general procedure described
above, 84 mg (53%) of 16c was obtained as a yellow solid: Rf =
0.46 (acetone–n-hexane, 1 : 10, v/v); mp 246–248 °C (acetone–n-
Methyl 3-amino-6,7-dichloro-4-cyano-5-hydroxybenzofuran-
2-carboxylate (17)
1
hexane); IR (KBr) νmax/cm−1 = 3231 (m), 1705 (s), 1621 (s); H
NMR (300 MHz, CDCl3 + DMSO-d6) δ = 6.18 (s, 1H), 6.74–6.82
(m, 2H), 7.25 (d, J = 8.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.76
(d, J = 8.3 Hz, 2H); 13C NMR (75.5 MHz, CDCl3 + DMSO-d6) δ =
103.2, 110.9, 111.0, 113.8, 123.6, 128.5, 131.0, 132.3, 134.8,
154.7, 156.0, 160.5, 162.0; HRMS (ESI) calcd for C15H9BrO3
[M+ + 1] 316.9813, found: 316.9802.
The
methyl
2-(7-hydroxy-4-phenyl-2H-chromen-2-ylidene)
acetate (15a, 147 mg, 0.5 mmol, 1 equiv.) was treated with
DDQ (227 mg, 1.0 mmol, 2 equiv.) in dioxane (5 ml) at 80 °C
for 2 h. Using the general procedure described above, 47 mg
(31%) of 17 was obtained as an off-white solid: Rf = 0.52
(MeOH–CHCl3, 1 : 4, v/v); mp > 250 °C (CHCl3–MeOH); IR
(KBr) νmax/cm−1 = 3374 (m), 3206 (w), 2229 (m), 1684 (s); 1H
NMR (300 MHz, DMSO-d6) δ = 3.87 (s, 3H), 5.65 (s, 1H) ppm;
13C NMR (50.3 MHz, DMSO-d6) δ = 51.5, 90.7, 101.9, 113.8,
119.6, 128.9, 137.3, 150.8, 154.0 ppm; m/z (ESI): 301 [M+ + H];
HRMS (ESI) calcd for C11H6Cl2N2O4 [M+ + 1] 300.9783, found
300.9760.
6-Chloro-7-hydroxy-4-phenyl-2H-chromen-2-one (16d)
The methyl 2-(6-chloro-7-hydroxy-4-phenyl-2H-chromen-2-
ylidene)acetate (15d, 164 mg, 0.5 mmol, 1 equiv.) was treated
with DDQ (227 mg, 1.0 mmol, 2 equiv.) in dioxane (5 ml) at
80 °C for 1 h. Using the general procedure described above,
71 mg (52%) of 16d was obtained as a yellow solid: Rf = 0.48
(acetone–n-hexane, 1 : 10, v/v); mp 226–228 °C {Llit.19 281 °C
General procedure for the synthesis of 18a–c
(ethyl acetate–heptane)} (acetone–n-hexane); IR (KBr) νmax
/
A mixture of the methyl 4-(methylthio)-2-oxo-6-aryl-2H-pyran-
cm−1 = 3201 (w), 1691 (s); 1H NMR (300 MHz, DMSO-d6) δ = 3-carboxylates 14 (1 mmol), the respective 1-tetralone
6.24 (s, 1H), 7.00 (s, 1H), 7.28 (s, 1H), 7.48–7.60 (m, 5H), 11.52 (1.2 mmol) and KOH (2.0 mmol) in dry DMF (10 ml) was
(brs, 1H, OH, D2O exchange); 13C NMR (75 MHz, DMSO-d6) δ = stirred at 90 °C for 12–24 h. Completion of the reaction was
104.4, 111.9, 112.0, 117.5, 127.4, 128.8, 129.4, 130.3, 135.0, monitored using TLC and on completion the reaction mixture
154.2, 154.8, 157.0, 160.1; HRMS (ESI) calcd for C15H9ClO3 was poured into crushed ice with vigorous stirring and finally
[M+ + 1] 273.0318; found: 273.0311.
neutralized with 10% HCl. The precipitate obtained was
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filtered and purified on a silica gel column using 20% CHCl3 2926 (s), 2857 (m), 1647 (m), 1562 (w); 1H NMR (300 MHz,
in n-hexane as the eluent to afford 18a–c as a mixture of cis- CDCl3): δ = 2.47–2.58 (m, 4H, cis + trans), 2.75–2.84 (m, 2H, cis
and trans-isomers.
+ trans), 3.68 (s, 3H, cis), 3.76 (s, 3H, trans), 4.96 (s, 1H, trans),
5.34 (s, 1H, cis), 7.14–7.44 (m, 8H, cis + trans), 7.70–7.78 (m,
1H, cis + trans) ppm; 13C NMR (75.5 MHz, CDCl3): δ = 23.1,
27.6, 50.5, 87.5, 112.0, 117.0, 122.5, 126.9, 127.5, 127.8, 128.0,
(Z/E)-Methyl 2-(4-(4-bromophenyl)-8-methoxy-5,6-dihydro-2H-
benzo[h]chromen-2-ylidene)acetate (18a)
A mixture of methyl 6-(4-bromophenyl)-4-(methylthio)-2-oxo- 128.4, 128.5, 128.6, 129.6, 137.1, 137.2, 147.2, 151.0, 165.3,
2H-pyran-3-carboxylate (14c, 353 mg, 1.0 mmol, 1 equiv.), 168.9 ppm; m/z (ESI): 331 [M + H+]; HRMS (ESI) calcd for
6-methoxy 1-tetralone (6c, 211 mg, 1.2 mmol, 1.2 equiv.) and C22H18O3 [M+ + 1] 331.1334, found 331.1372.
KOH (112 mg, 2.0 mmol, 2 equiv.) in dry DMF (10 ml) was
General procedure for the synthesis of 19a–c
stirred at 90 °C for 12 h. Using the general procedure
described above, 153 mg (35%) of 18a was obtained as a (Z/E)-Methyl 2-(4-aryl-5,6-dihydro-2H-benzo[h]chromen-2-
mixture of cis- and trans-isomers, as a red oil: Rf = 0.54 ylidene)acetates (18a–c) were treated with 2.0 mmol of DDQ in
(CHCl3–n-hexane, 7 : 3, v/v); IR (KBr) νmax/cm−1 = 2952 (m), AcOH at room temp for 1–2 h. After completion, the reaction
1
2861 (w), 2337 (m), 1605 (m); H NMR (300 MHz, CDCl3): δ = mixture was filtered and the filtrate was collected and evapor-
2.42–2.51 (m, 4H, cis + trans), 2.71–2.80 (m, 4H, cis + trans), ated to dryness. Thereafter, the crude obtained was purified
3.68 (s, 3H, cis), 3.74 (s, 3H, trans), 3.84 (s, 6H, cis + trans), 4.93 through a silica gel column using 40% CHCl3 in hexane as the
(s, 3H, trans), 5.31 (s, 1H, cis), 6.71 (s, 2H, cis + trans), eluent to afford 19a–c.
6.78–6.92 (m, 1H, cis + trans), 7.12–7.24 (m, 2H, cis + trans),
4-(4-Bromophenyl)-8-methoxy-5,6-dihydro-2H-benzo[h]-
chromen-2-one (19a)
7.51–7.68 (m, 4H, cis + trans) ppm; 13C NMR (75.5 MHz,
CDCl3): δ = 26.6, 28.1, 51.8, 55.3, 87.3, 112.1, 112.1, 113.5,
116.2, 124.3, 127.2, 129.5, 129.7, 130.2, 130.6, 131.4, 131.6, The (Z/E)-methyl 2-(4-(4-bromophenyl)-8-methoxy-5,6-dihydro-
140.0, 144.8, 146.4, 157.6, 159.3, 168.4 ppm; m/z (ESI): 439 2H-benzo[h]chromen-2-ylidene)-acetate (18a, 219 mg, 0.5 mmol,
[M + H+]; HRMS (ESI) calcd for C23H19BrO4 [M+ + 1] 439.0545, 1 equiv.) was treated with DDQ (227 mg, 1.0 mmol, 2 equiv.) in
found 439.0507.
glacial acetic acid (5 ml) for 2 h. Using the general procedure
described above, 99 mg (52%) of 19a was obtained as a yellow
solid: Rf = 0.70 (CHCl3–n-hexane, 7 : 3, v/v); mp 176–178 °C
(CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 2925 (w), 2856 (w),
(Z/E)-Methyl 2-(4-(furan-2-yl)-5,6-dihydro-2H-benzo[h]
chromen-2-ylidene)acetate (18b)
A mixture of methyl 6-(furan-2-yl)-4-(methylthio)-2-oxo-2H- 1712 (m); 1H NMR (300 MHz, CDCl3) δ = 2.51–2.60 (m, 2H),
pyran-3-carboxylate (14f, 266 mg, 1.0 mmol, 1 equiv.), 1-tetra- 2.76–2.85 (m, 2H), 3.85 (s, 3H), 6.09 (s, 1H), 6.73 (s, 1H), 6.85
lone (6a, 0.146 ml, 1.2 mmol, 1.2 equiv.) and KOH (112 mg, (d, J = 8.7 Hz, 1H), 7.14–7.24 (m, 2H), 7.56–7.63 (m, 2H) 7.85
2.0 mmol, 2 equiv.) in dry DMF (10 ml) was stirred at 90 °C for (d, J = 8.6 Hz, 1H) ppm; 13C NMR (50.3 MHz, CDCl3) δ = 23.0,
15 h. Using the general procedure described above, 102 mg 27.9, 55.4, 109.3, 111.2, 112.2, 113.6, 121.1, 123.5, 125.6, 129.3,
(32%) of 18b was obtained as a mixture of cis- and trans- 131.9, 135.4, 139.6, 155.9, 157.5, 161.5 ppm; m/z (ESI): 383
isomers, as a red oil: Rf = 0.52 (CHCl3–n-hexane, 7 : 3, v/v); IR [M+ + H]; HRMS (ESI) calcd for C20H15BrO3 [M+ + 1] 383.0283,
1
(KBr) νmax/cm−1 = 2932 (m), 2854 (w), 1734 (m), 1632 (w); H found 383.0250.
NMR (300 MHz, CDCl3): δ = 2.89 (s, 8H, cis + trans), 3.72 (s,
3H, trans), 3.75 (s, 3H, cis), 5.01 (s, 1H, trans), 5.32 (s, 1H, cis),
4-(Furan-2-yl)-5,6-dihydro-2H-benzo[h]chromen-2-one (19b)
6.48–6.61 (m, 2H, cis + trans), 6.68 (d, J = 3.4 Hz, 1H, trans), The (Z/E)-methyl 2-(4-(furan-2-yl)-5,6-dihydro-2H-benzo[h]-
6.74 (d, J = 3.4 Hz, 1H, cis), 7.14–7.38 (m, 6H, cis + trans), 7.54 chromen-2-ylidene)acetate (18b, 160 mg, 0.5 mmol, 1 equiv.)
(d, J = 1.3 Hz, 2H, cis + trans), 7.64–7.71 (m, 1H, cis), 8.13 (d, was treated with DDQ (227 mg, 1.0 mmol, 2 equiv.) in glacial
J = 5.1 Hz, 2H, cis + trans) ppm; 13C NMR (75.5 MHz, CDCl3): δ acetic acid (5 ml) for 2 h. Using the general procedure
= 23.0, 27.4, 50.5, 87.8, 109.9, 111.9, 112.4, 113.8, 122.4, 126.9, described above, 54 mg (41%) of 19b was obtained as a yellow
127.3, 128.5, 129.5, 134.4, 136.7, 143.8, 150.1, 151.1, 164.4, solid: Rf = 0.39 (CHCl3–n-hexane, 7 : 3, v/v); mp 144–146 °C
168.4 ppm; m/z (ESI): 321 [M + H+]; HRMS (ESI) calcd for (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 2924 (m), 1630 (m); 1H
C20H16O4 [M+ + 1] 321.1127, found 321.1119.
NMR (300 MHz, CDCl3) δ = 2.94–3.00 (m, 4H), 6.57 (s, 2H),
6.86 (d, J = 3.0 Hz, 1H), 7.21–7.35 (m, 3H), 7.60–7.64 (m, 1H),
7.90 (d, J = 4.6 Hz, 1H) ppm; 13C NMR (75.5 MHz, CDCl3) δ =
23.1, 27.3, 108.3, 109.6, 112.3, 114.3, 123.7, 127.1, 127.5, 128.3,
(Z/E)-Methyl 2-(4-phenyl-5,6-dihydro-2H-benzo[h]chromen-
2-ylidene)acetate (18c)
A mixture of methyl 4-(methylthio)-2-oxo-6-phenyl-2H-pyran-3- 130.3, 136.9, 144.9, 148.9, 155.4, 162.0 ppm; m/z (ESI): 265
carboxylate (14a, 276 mg, 1.0 mmol, 1 equiv.), 1-tetralone (6a, [M+ + H]; HRMS (ESI) calcd for C17H12O3 [M+ + 1] 265.0865,
0.146 ml, 1.2 mmol, 1.2 equiv.) and KOH (112 mg, 2.0 mmol, 2 found 265.0868.
equiv.) in dry DMF (10 ml) was stirred at 90 °C for 24 h. Using
the general procedure described above, 113 mg (34%) of 18c
4-Phenyl-5,6-dihydro-2H-benzo[h]chromen-2-one (19c)
was obtained as a mixture of cis- and trans-isomers, as a red The(Z/E)-methyl 2-(4-phenyl-5,6-dihydro-2H-benzo[h]chromen-
oil: Rf = 0.57 (CHCl3–n-hexane, 7 : 3, v/v); IR (KBr) νmax/cm−1
=
2-ylidene)acetate (18c, 165 mg, 0.5 mmol, 1 equiv.) was treated
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with DDQ (227 mg, 1.0 mmol, 2 equiv.) in glacial acetic acid (s, 1H, cis), 6.52 (s, 1H, trans), 6.56 (s, 1H, trans), 7.05 (s, 1H,
(5 ml) for 1 h. Using the general procedure described above, cis), 7.45–7.68 (m, 18H, cis + trans), 7.90–8.01 (m, 4H, cis +
65 mg (48%) of 19c was obtained as a yellow solid: Rf = 0.50 trans), 8.15 (d, J = 7.6 Hz, 1H, trans), 8.29 (d, J = 8.2 Hz, 1H,
(CHCl3–n-hexane, 7 : 3, v/v); mp 154–156 °C (CHCl3–n-hexane); trans) ppm; 13C NMR (75.5 MHz, CDCl3): δ = 66.4, 67.2, 105.9,
IR (KBr) νmax/cm−1 = 2922 (m), 2858 (w), 1750 (m); 1H NMR 106.0, 112.1, 112.9, 113.2, 117.8, 119.1, 124.7, 124.7, 125.0,
(300 MHz, CDCl3) δ = 2.56–2.65 (m, 2H), 2.79–2.88 (m, 2H), 125.9, 126.1, 126.4, 126.4, 126.5, 127.2, 127.4, 128.7, 129.1,
6.20 (s, 1H), 7.16–7.49 (m, 8H), 7.88–7.94 (m, 1H) ppm; 129.9, 130.0, 130.1, 130.2, 130.3, 130.4, 131.0, 133.7, 133.8,
13C NMR (75.5 MHz, CDCl3) δ = 23.0, 27.6, 111.7, 112.8, 123.7, 135.5, 135.6, 142.9, 143.7, 158.0, 158.2, 166.3, 168.0 ppm; m/z
127.2, 127.7, 128.3, 128.7, 129.2, 130.3, 136.4, 137.3, 155.1, (ESI): 322.2 [M + H+]; HRMS (ESI) calcd for C23H15NO [M+ + 1]
158.6, 161.9 ppm; m/z (ESI): 275 [M+ + H]; HRMS (ESI) calcd 322.1232, found 322.1237.
for C19H14O2 [M+ + 1] 275.1072, found 275.1067.
(Z/E)-2-(4,6-Bis(4-bromophenyl)-2H-pyran-2-ylidene)
4-(4-Bromophenyl)-8-methoxy-2H-benzo[h]chromen-2-one
acetonitrile (23b)
(20a)
A mixture of 6-(4-bromophenyl)-4-(methylthio)-2-oxo-2H-pyran-
4-(4-Bromophenyl)-8-methoxy-5,6-dihydro-2H-benzo[h]chromen- 3-carbonitrile (21b, 320 mg, 1.0 mmol, 1 equiv.), 1-(4-bromo-
2-one (19a, 76 mg, 0.2 mmol, 1 equiv.) was refluxed with phenyl)ethanone (22b, 199 mg, 1.0 mmol, 1 equiv.) and KOH
6 mmol of DDQ (272 mg, 1.2 mmol, 6 equiv.) in benzene (84 mg, 1.5 mmol, 1.5 equiv.) in dry DMF (15 ml) was stirred at
(5 ml) at 90 °C for 8 h. After completion, the reaction mixture 90 °C for 24 h. Using the general procedure described above,
was filtered and the filtrate was collected and evaporated to 204 mg (48%) of 23b was obtained as a mixture of cis- and
dryness. The crude 20a obtained was purified by column trans-isomers, as a red oil: Rf = 0.64 (CHCl3–n-hexane, 7 : 3,
chromatography on a silica gel using 30% CHCl3 in n-hexane v/v); IR (KBr) νmax/cm−1 = 2925 (w), 2872 (w), 2195 (m), 1649
1
as the eluent to afford 40 mg (52%) of 4-(4-bromophenyl)- (m); H NMR (300 MHz, CDCl3): δ = 4.38 (s, 1H, cis), 4.67 (s,
8-methoxy-2H-benzo[h]chromen-2-one (20a) was obtained as 1H, trans), 6.48 (s, 1H, cis), 6.54 (s, 1H, trans), 6.58 (s, 1H, cis),
an off-white solid: Rf = 0.53 (CHCl3–n-hexane, 7 : 3, v/v); mp 6.93 (s, 1H, trans), 7.41–7.63 (m, 14H, cis + trans), 7.73 (d, J =
194–196 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 3013 (w), 8.6 Hz, 2H, cis) ppm; 13C NMR (75.5 MHz, CDCl3): δ = 67.2,
1718 (w), 1634 (m); 1H NMR (300 MHz, CDCl3) δ = 3.96 (s, 3H), 68.1, 100.6, 100.9, 112.7, 113.7, 117.7, 118.8, 125.3, 126.6,
6.36 (s, 1H), 7.15 (d, J = 2.2 Hz, 1H), 7.27–7.33 (m, 1H), 127.2, 127.4, 127.5, 127.6, 129.4, 129.8, 132.2, 132.2, 132.4,
7.34–7.41 (m, 3H), 7.51 (d, J = 8.8 Hz, 1H), 7.69 (d, J = 8.4 Hz, 134.0, 134.2, 141.9, 142.4, 155.9, 156.2, 165.5, 167.1 ppm; m/z
1H), 8.51 (d, J = 9.2 Hz, 1H) ppm; 13C NMR (75.5 MHz, CDCl3) (ESI): 427 [M+ + H]; HRMS (ESI) calcd for C19H11Br2NO
δ = 55.4, 106.2, 112.2, 113.2, 118.2, 119.6, 122.7, 123.0, 124.0, [M+ + 1] 427.9286, found 427.9328.
124.5, 130.1, 132.1, 134.6, 136.8, 151.8, 152.7, 155.5, 160.2,
(Z/E)-2-(4,6-Di-p-tolyl-2H-pyran-2-ylidene)acetonitrile (23c)
160.7 ppm; m/z (ESI): 381 [M+ + H]; HRMS (ESI) calcd for
C20H13BrO3 [M+ + 1] 381.0126, found 381.0112.
A mixture of 4-(methylthio)-2-oxo-6-(p-tolyl)-2H-pyran-3-carbo-
nitrile (21c, 257 mg, 1.0 mmol, 1 equiv.), 1-(4-methylphenyl)
ethanone (22c, 0.133 ml, 1.0 mmol, 1 equiv.) and KOH (84 mg,
General procedure for the synthesis of 23a–f
A mixture of the 4-(methylthio)-2-oxo-6-aryl-2H-pyran-3-carbo- 1.5 mmol, 1.5 equiv.) in dry DMF (15 ml) was stirred at 90 °C
nitriles 21 (1 mmol), substituted acetophenones 22 (1.2 mmol) for 24 h. Using the general procedure described above, 111 mg
and KOH (1.5 mmol) in dry DMF (15 ml) were stirred at 90 °C (37%) of 23c was obtained as a mixture of cis- and trans-
for 24 h. Completion of the reaction was monitored using TLC isomers, as a red oil: Rf = 0.64 (CHCl3–n-hexane, 7 : 3, v/v); IR
1
and on completion the reaction mixture was poured into (KBr) νmax/cm−1 = 2923 (m), 2856 (w), 2193 (m), 1646 (w); H
crushed ice with vigorous stirring and finally neutralized with NMR (300 MHz, CDCl3): δ = 2.40 (s, 6H), 4.29 (s, 1H, cis), 4.57
10% HCl. The precipitate obtained was filtered and purified (s, 1H, trans), 6.43 (s, 1H, cis), 6.58 (s, 1H, trans), 6.90 (s, 1H,
on a silica gel column using 30% CHCl3 in n-hexane as the cis), 6.91 (s, 1H, trans), 7.20–7.29 (m, 10H, cis + trans),
eluent to afford 23a–f as a mixture of cis- and trans-isomers.
7.42–7.54 (m, 4H, cis + trans), 7.62 (d, J = 8.1 Hz, 2H, cis), 7.76
(d, J = 8.1 Hz, 2H, trans) ppm; 13C NMR (75.5 MHz, CDCl3): δ =
21.3, 21.3, 21.4, 21.5, 65.3, 66.1, 100.0, 100.3, 111.2, 112.1,
118.5, 119.6, 125.1, 125.1, 125.9, 126.1, 128.4, 128.7, 129.5,
(Z/E)-2-(6-(Naphthalen-1-yl)-4-phenyl-2H-pyran-2-ylidene)-
acetonitrile (23a)
A mixture of 4-(methylthio)-2-oxo-6-phenyl-2H-pyran-3-carboni- 129.6, 129.6, 129.8, 132.9, 133.1, 140.4, 140.5, 141.1, 141.1,
trile (21a, 243 mg, 1.0 mmol, 1 equiv.), 1-(naphthalen-1-yl) 143.3, 143.9, 156.8, 157.1, 166.4, 168.1 ppm; m/z (ESI): 300
ethanone (22a, 170 mg, 1.0 mmol, 1 equiv.) and KOH (84 mg, [M+ + H]; HRMS (ESI) calcd for C21H17NO [M+ + 1] 300.1388,
1.5 mmol, 1.5 equiv.) in dry DMF (15 ml) was stirred at 90 °C found 300.1377.
for 24 h. Using the general procedure described above, 122 mg
(Z/E)-2-(4,6-Di(naphthalen-2-yl)-2H-pyran-2-ylidene)acetonitrile
(38%) of 23a was obtained as a mixture of cis- and trans-
(23d)
isomers, as a red oil: Rf = 0.59 (CHCl3–n-hexane, 7 : 3, v/v); IR
(KBr) νmax/cm−1 = 2926 (w), 2215 (s), 1649 (s); 1H NMR
A
mixture of 4-(methylthio)-6-(naphthalen-2-yl)-2-oxo-2H-
(300 MHz, CDCl3): δ = 4.39 (s, 1H, trans), 4.61 (s, 1H, cis), 6.49 pyran-3-carbonitrile (21d, 293 mg, 1.0 mmol, equiv.),
1
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1-(naphthalen-2-yl)ethanone (22d, 170 mg, 1.0 mmol, 1 equiv.) 2-(6-Isopropyl-4-(4-methoxyphenyl)-3-methyl-5-phenyl-2H-
and KOH (84 mg, 1.5 mmol, 1.5 equiv.) in dry DMF (15 ml) pyran-2-ylidene)acetonitrile (23f)
was stirred at 90 °C for 24 h. Using the general procedure
A
mixture of 6-(4-methoxyphenyl)-5-methyl-4-morpholino-
described above, 149 mg (40%) of 23d was obtained as a
mixture of cis- and trans-isomers, as a red oil: Rf = 0.51
(CHCl3–n-hexane, 7 : 3, v/v); IR (KBr) νmax/cm−1 = 2928 (w),
2860 (w), 2194 (s), 1647 (m); 1H NMR (300 MHz, CDCl3): δ =
4.36 (s, 1H, cis), 4.70 (s, 1H, trans), 6.55 (s, 1H, cis), 6.85 (s, 2H,
cis + trans), 7.06 (s, 1H, trans), 7.48–7.65 (m, 10H, cis + trans),
7.79–8.10 (m, 16H, cis + trans), 8.23 (s, 1H, trans), 8.39 (s, 1H,
cis) ppm; 13C NMR (50.3 MHz, CDCl3): δ = 66.1, 67.0, 100.8,
101.0, 112.2, 113.2, 118.3, 119.3, 121.6, 121.7, 122.9, 123.0,
123.6, 124.2, 125.0, 125.3, 125.7, 125.8, 126.7, 126.9, 127.2,
127.4, 127.5, 127.7, 128.0, 128.2, 128.5, 128.5, 128.6, 128.7,
128.9, 129.0, 132.5, 132.7, 132.8, 133.1, 133.8, 133.9, 134.0,
142.7, 143.3, 156.3, 156.5, 165.9, 167.6 ppm; m/z (ESI): 372
[M+ + H]; HRMS (ESI) calcd for C27H17NO [M+ + 1] 372.1388,
found 372.1387.
2-oxo-2H-pyran-3-carbonitrile (I, 326 mg, 1.0 mmol, 1 equiv.),
3-methyl-1-phenyl-butan-2-one (22f, 0.162 ml, 1.0 mmol,
1 equiv.) and powdered KOH (84 mg, 1.5 mmol, 1.5 equiv.) in
dry DMF (5 ml) was stirred at 90 °C for 24 h. Using the general
procedure described above, 175 mg (49%) of 23f was obtained
as a yellow solid: Rf = 0.49 (CHCl3–n-hexane, 7 : 3, v/v); mp
183–185 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 3022 (w),
1
2930 (w), 2199 (m); H NMR (300 MHz, CDCl3) δ = 1.21 (d, J =
6.8 Hz, 6H), 1.67 (s, 3H), 2.55–2.65 (m, 1H), 3.70 (s, 3H), 4.24
(s, 1H), 6.61–6.76 (m, 4H), 6.82–6.91 (m, 2H), 7.08–7.16 (m,
3H) ppm; 13C NMR (50.3 MHz, CDCl3) δ = 14.8, 18.4, 20.2,
30.2, 55.0, 62.9, 113.2, 116.9, 119.9, 126.9, 127.9, 128.9, 130.0,
130.3, 135.3, 158.6, 160.1, 167.4 ppm; m/z (ESI): 358 [M+ + H];
HRMS (ESI) calcd forC24H23NO2 [M+ + 1] 358.1807, found
358.1800.
(Z/E)-2-(4,6-Di(thiophen-2-yl)-2H-pyran-2-ylidene)acetonitrile
(23e)
General procedure for the synthesis of 24a–f
The functionalized 2H-pyran-2-ylidene-acetonitriles (23a–f)
were treated with 2.0 mmol of DDQ in AcOH at room temp for
5–6 h. After completion, the reaction mixture was filtered and
the filtrate was collected and evaporated to dryness. Thereafter,
the crude obtained was purified through column chromato-
graphy on silica gel using 50% CHCl3 in hexane as the eluent
to afford highly functionalized 2H-pyran-2-ones 24a–f.
A mixture of 4-(methylthio)-2-oxo-6-(thiophen-2-yl)-2H-pyran-
3-carbonitrile (21e, 248 mg, 1.0 mmol, 1 equiv.), 1-(thiophen-
2-yl)ethanone (22e, 0.107 ml, 1.0 mmol, 1 equiv.) and KOH
(84 mg, 1.5 mmol, 1.5 equiv.) in dry DMF (15 ml) was stirred at
90 °C for 24 h. Using the general procedure described above,
110 mg (39%) of 23e was obtained as a mixture of cis-
and trans-isomers, as a red oil: Rf = 0.48 (CHCl3–n-hexane,
7 : 3, v/v); IR (KBr) νmax/cm−1 = 2922 (m), 2859 (w), 2191 (w),
6-(Naphthalen-1-yl)-4-phenyl-2H-pyran-2-one (24a)
1
1629 (m); H NMR (300 MHz, CDCl3): δ = 4.31 (s, 1H, cis), 4.58
The (Z/E)-2-(6-(naphthalen-1-yl)-4-phenyl-2H-pyran-2-ylidene)-
acetonitrile (23a, 161 mg, 0.5 mmol, 1 equiv.) was treated with
DDQ (227 mg, 1.0 mmol, 2 equiv.) in glacial acetic acid (5 ml)
for 6 h. Using the general procedure described above, 70 mg
(47%) of 24a was obtained as a yellow solid: Rf = 0.40 (CHCl3–
n-hexane, 7 : 3, v/v); mp 126–128 °C (CHCl3–n-hexane); IR (KBr)
νmax/cm−1 = 2926 (m), 1715 (s), 1627 (m), 1538 (m); 1H NMR
(300 MHz, CDCl3) δ = 6.58 (d, J = 1.3 Hz, 1H), 6.85 (d, J =
1.3 Hz, 1H), 7.48–7.79 (m, 9H), 7.88–8.01 (m, 2H), 8.22–8.29
(m, 1H) ppm; 13C NMR (50.3 MHz, CDCl3) δ = 106.5, 109.3,
124.9, 125.0, 126.5, 126.8, 127.4, 127.8, 128.7, 129.3, 130.4,
130.8, 131.2, 133.8, 135.8, 155.4, 161.8, 163.0 ppm; m/z (ESI):
299 [M+ + H]; HRMS (ESI) calcd for C21H14O2 [M+ + 1]
299.1072, found 299.1078.
(s, 1H, trans), 6.39–6.44 (m, 3H, cis + trans), 6.85 (d, J = 1.3 Hz,
1H, trans), 7.07–7.16 (m, 4H, cis + trans), 7.38–7.48 (m, 6H, cis
+ trans), 7.64 (d, J = 2.8 Hz, 2H, trans) ppm; 13C NMR
(50.3 MHz, CDCl3): δ = 66.2, 67.0, 98.7, 98.9, 109.0, 110.0,
126.6, 127.4, 128.3, 128.5, 128.6, 134.6, 139.1, 152.3,
165.1 ppm; m/z (ESI): 284 [M+ + H]; HRMS (ESI) calcd for
C15H9NOS2 [M+ + 1] 284.0204, found 284.0208.
6-(4-Methoxyphenyl)-5-methyl-4-morpholino-2-oxo-2H-pyran-
3-carbonitrile (I)
In order to synthesize 23f, the methylsulfanyl group of 6-(4-
methoxyphenyl)-5-methyl-4-(methylthio)-2-oxo-2H-pyran-3-
carbonitrile 21f20 was replaced by morpholine by reacting
lactone 21f (287 mg, 1.0 mmol) with morpholine (0.1 ml,
1.2 mmol) in methanol (10 ml) at reflux temperature for 8 h to
give the precursor 6-(4-methoxyphenyl)-5-methyl-4-morpho-
4,6-Bis(4-bromophenyl)-2H-pyran-2-one (24b)
lino-2-oxo-2H-pyran-3-carbonitrile (I) in a quantitative yield of The (Z/E)-2-(4,6-bis(4-bromophenyl)-2H-pyran-2-ylidene)aceto-
310 mg (95%). nitrile (23b, 213 mg, 0.5 mmol, 1 equiv.) was treated with DDQ
Yellow solid: Rf = 0.56 (MeOH–CHCl3, 1 : 25 v/v); mp (227 mg, 1.0 mmol, 2 equiv.) in glacial acetic acid (5 ml) for
164–166 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1 = 3024 (w), 5 h. Using the general procedure described above, 83 mg
2215 (w), 1703 (m); 1H NMR (300 MHz, CDCl3): δ = 2.10 (s, (41%) of 24b was obtained as a yellow solid: Rf = 0.48 (CHCl3–
3H), 3.58–3.75 (m, 4H), 3.82–3.94 (m, 7H), 6.95 (d, J = 8.8 Hz, n-hexane, 7 : 3, v/v); mp 216–218 °C (CHCl3–n-hexane); IR (KBr)
2H), 7.53 (d, J = 8.8 Hz, 2H); 13C NMR (50.3 MHz, CDCl3): δ = νmax/cm−1 = 2920 (w), 1691 (s), 1535 (w); 1H NMR (300 MHz,
17.7, 51.8, 55.5, 67.0, 80.8, 106.6, 113.9, 116.5, 124.0, 131.5, CDCl3) δ = 6.45 (s, 1H), 6.88 (s, 1H), 7.45–7.68 (m, 6H), 7.75 (d,
161.9, 162.2, 168.1 ppm; m/z (ESI): 327 [M+ + H]; HRMS (ESI) J = 8.6 Hz, 2H) ppm; 13C NMR (50.3 MHz, CDCl3) δ = 101.1,
calcd for C18H18N2O4 [M+ + 1] 327.1345, found 327.1344.
109.7, 125.7, 127.2, 128.0, 128.2, 129.6, 130.3, 132.3, 132.6,
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134.3, 137.2, 154.2, 159.6, 162.0 ppm; HRMS (ESI) calcd for (CHCl3–n-hexane, 7 : 3, v/v); mp 172–174 °C (CHCl3–n-hexane);
C17H10Br2O2 [M+ + 1] 404.9126, found 404.9313.
IR (KBr) νmax/cm−1 = 2974 (w), 2928 (w), 1707 (s); 1H NMR
(300 MHz, CDCl3) δ = 1.19 (d, J = 6.8 Hz, 6H), 1.92 (s, 3H),
2.60–2.72 (m, 1H), 3.71 (s, 3H), 6.65–6.92 (m, 4H), 7.83–7.92
4,6-Di-p-tolyl-2H-pyran-2-one (24c)
The (Z/E)-2-(4,6-di-p-tolyl-2H-pyran-2-ylidene)acetonitrile (23c, (m, 2H), 7.11–7.17 (m, 3H) ppm; 13C NMR (50 MHz, CDCl3) δ =
150 mg, 0.5 mmol, 1 equiv.) was treated with DDQ (227 mg, 14.5, 20.3, 30.4, 30.9, 55.2, 113.1, 113.9, 117.9, 118.8, 127.0,
1.0 mmol, 2 equiv.) in glacial acetic acid (5 ml) for 5 h. Using 127.8, 128.0, 128.3, 128.9, 129.6, 130.4, 130.7, 137.4, 141.3,
the general procedure described above, 65 mg (47%) of 24c 152.2, 158.7 ppm; m/z (ESI): 335 [M+ + H]; HRMS (ESI) calcd
was obtained as a yellow solid: Rf = 0.38 (CHCl3–n-hexane, 7 : 3, for C22H22O3 [M+ + 1] 335.1647, found 335.1642.
v/v); mp 163–165 °C (CHCl3–n-hexane); IR (KBr) νmax/cm−1
=
2928 (w), 1696 (m), 1630 (m), 1512 (m); 1H NMR (300 MHz,
CDCl3) δ = 2.41 (s, 3H), 2.43 (s, 3H), 6.43 (s, 1H), 6.92 (s, 1H),
7.22–7.35 (m, 4H), 7.55 (d, J = 8.1 Hz, 1H), 7.79 (d, J = 8.1 Hz,
1H) ppm; 13C NMR (75.5 MHz, CDCl3) δ = 21.4, 21.5, 100.6,
108.1, 125.7, 126.6, 128.9, 129.7, 129.9, 133.2, 141.1, 141.4,
155.5, 160.5, 163.0 ppm; m/z (ESI): 277 [M+ + H]; HRMS (ESI)
calcd for C19H16O2 [M+ + 1] 277.1229, found 277.1234.
Acknowledgements
We gratefully acknowledge financial support by the CSIR
under Network Projects THUNDER (BSC0102) and HOPE
(BSC0114), New-Delhi, India. The spectroscopic data provided
by SAIF, CDRI is gratefully acknowledged. The CSIR-CDRI com-
munication number for the manuscript is 8477.
4,6-Di(naphthalen-2-yl)-2H-pyran-2-one (24d)
The (Z/E)-2-(4,6-di(naphthalen-2-yl)-2H-pyran-2-ylidene)aceto-
nitrile (23d, 186 mg, 0.5 mmol, 1 equiv.) was treated with DDQ
(227 mg, 1.0 mmol, 2 equiv.) in glacial acetic acid (5 ml) for
6 h. Using the general procedure described above, 75 mg
(43%) of 24d was obtained as a yellow solid: Rf = 0.36 (CHCl3–
n-hexane, 7 : 3, v/v); mp 166–168 °C (CHCl3–n-hexane); IR (KBr)
Notes and references
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Natural Coumarins: Occurrence, Chemistry, and Biochemistry,
Wiley, New York, 1982; (b) A. Goel and V. J. Ram, Tetrahe-
dron, 2009, 65, 7865–7913.
2 D. J. Hadjipavlou-Litina, K. E. Litinas and D. N. Nicolaides,
Curr. Pharm. Des., 2004, 10, 3813–3833.
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Chem. Rev., 2004, 104, 3059–3077; (b) J. Gordo, J. Avo,
A. J. Parola, J. C. Lima, A. Pereira and P. S. Branco, Org.
Lett., 2011, 13, 5112–5115.
4 (a) P. N. P. Rao, M. J. Uddin and E. E. Knaus, J. Med. Chem.,
2004, 47, 3972–3990; (b) M. Riveiro, K. N. De, A. Moglioni,
R. Vázquez, F. Monczor, C. Shayo and C. Davio, Curr. Med.
Chem., 2010, 17, 1325–1328; (c) S. B. Combes, P. Barbier,
S. Douillard, A. McLeer-Florin, V. R. Bourgarel-Rey,
J.-T. Pierson, A. Y. Fedorov, J.-P. Finet, J. Boutonnat and
V. Peyrot, J. Med. Chem., 2011, 54, 3153–3162.
5 (a) R. K. Dieter and J. R. Fishpaugh, J. Org. Chem., 1983, 48,
4439–4441; (b) G. Jones, Org. React., 1967, 15, 204–599;
(c) G. Brufola, F. Fringuelli, O. Piermatti and F. Pizzo,
Heterocycles, 1996, 43, 1257–1266; (d) J. Smodiš and
B. Stanovnik, Tetrahedron, 1998, 54, 9799–9810.
6 (a) T. Luo and S. L. Schreiber, Angew. Chem., Int. Ed., 2007,
46, 8250–8253; (b) L. Ackermann, J. Pospech, K. Graczyk
and K. Rauch, Org. Lett., 2012, 14, 930–933.
1
νmax/cm−1 = 2920 (m), 2853 (m), 1708 (m), 1531 (w); H NMR
(300 MHz, CDCl3) δ = 6.64 (d, J = 1.2 Hz, 1H), 7.24 (d, J =
1.2 Hz, 1H), 7.54–7.63 (m, 4H), 7.72–7.80 (m, 1H), 7.84–8.03
(m, 7H), 8.20 (s, 1H), 8.53 (s, 1H) ppm; 13C NMR (75.5 MHz,
CDCl3) δ = 101.7, 107.9, 108.2, 116.0, 122.6, 129.9, 129.7, 130.1,
132.2, 138.2, 138.5, 139.7, 141.0, 152.5, 153.2, 153.3, 158.8,
159.5, 169.2 ppm.
4,6-Di(thiophen-2-yl)-2H-pyran-2-one (24e)
The
(Z/E)-2-(4,6-di(thiophen-2-yl)-2H-pyran-2-ylidene)aceto-
nitrile (23e, 142 mg, 0.5 mmol, 1 equiv.) was treated with DDQ
(227 mg, 1.0 mmol, 2 equiv.) in glacial acetic acid (5 ml) for
6 h. Using the general procedure described above, 50 mg
(38%) of 24e was obtained as a yellow solid: Rf = 0.32 (CHCl3–
n-hexane, 7 : 3, v/v); mp 158–160 °C {lit.21 158 °C} (CHCl3–n-
hexane); IR (KBr) νmax/cm−1 = 2913 (m), 2139 (w), 1705 (m),
1
1651 (m); H NMR (300 MHz, CDCl3) δ = 6.39 (d, J = 1.3 Hz,
1H), 6.76 (d, J = 1.3 Hz, 1H), 7.11–7.22 (m, 2H), 7.48 (d, J =
5.0 Hz, 1H), 7.51–7.59 (m, 2H), 7.64–7.69 (m, 1H) ppm; 13C
NMR (75.5 MHz, CDCl3) δ = 99.1, 105.5, 127.7, 128.0, 128.4,
128.7, 129.1, 129.8, 135.1, 138.8, 148.1, 156.0, 161.8 ppm; m/z
(ESI): 261 [M+ + H]; HRMS (ESI) calcd for C13H8O2S2 [M+ + 1]
261.0044, found 261.0046.
7 (a) A. K. Chatterjee, F. D. Toste, S. D. Goldberg and
R. H. Grubbs, Pure Appl. Chem., 2003, 75, 421–425;
(b) B. M. Trost, F. D. Toste and K. Greenman, J. Am. Chem.
Soc., 2003, 125, 4518–4526; (c) K. Nakai, T. Kurahashi and
S. Matsubara, J. Am. Chem. Soc., 2011, 133, 11066–11068;
(d) S. Kim, D. Kang, C.-H. Lee and P. Ho. Lee, J. Org. Chem.,
2012, 77, 6530–6537; (e) D. K. Rayabarapu, P. Shukla and
C. H. Cheng, Org. Lett., 2003, 5, 4903–4906; (f) T. N. Van,
6-Isopropyl-4-(4-methoxyphenyl)-3-methyl-5-phenyl-2H-pyran-
2-one (24f)
The (Z/E)-2-(6-isopropyl-4-(4-methoxyphenyl)-3-methyl-5-phenyl-
2H-pyran-2-ylidene)acetonitrile (23f, 179 mg, 0.5 mmol,
1 equiv.) was treated with DDQ (227 mg, 1.0 mmol, 2 equiv.) in
glacial acetic acid (5 ml) for 5 h. Using the general procedure
described above, 65 mg (39%) of 24f as a yellow solid: Rf = 0.40
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