An advanced and novel one-pot synthetic method for diverse benzo[c]chromen-6-ones by transition-metal free mild base-promoted domino reactions of substituted 2-hydroxychalcones with β-ketoesters and its application to polysubstituted terphenyls

Article abstract of DOI:10.1039/c3ob41800f

Novel and efficient one-pot syntheses of a variety of benzo[c]chromen-6-one derivatives were accomplished using Cs₂CO₃-promoted reactions between substituted 2-hydroxychalcones and β-ketoesters. These reactions involved domino Michael addition/intramolecular aldol/oxidative aromatization/lactonization and provided a rapid synthetic route for the production of biologically interesting novel benzo[c]chromen-6-one molecules bearing several different substituents on benzene rings. As an application of this methodology, several synthesized benzo[c]chromen-6-ones were transformed into highly functionalized novel terphenyls.

Full text of DOI:10.1039/c3ob41800f

Organic &
Biomolecular Chemistry
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PAPER
An advanced and novel one-pot synthetic method
for diverse benzo[c]chromen-6-ones by transition-
metal free mild base-promoted domino reactions
of substituted 2-hydroxychalcones with
β-ketoesters and its application to polysubstituted
terphenyls†
Cite this: Org. Biomol. Chem., 2014,
12, 919
Tej Narayan Poudel and Yong Rok Lee*
Novel and efficient one-pot syntheses of a variety of benzo[c]chromen-6-one derivatives were accom-
plished using Cs2CO3-promoted reactions between substituted 2-hydroxychalcones and β-ketoesters.
These reactions involved domino Michael addition/intramolecular aldol/oxidative aromatization/lactoniza-
tion and provided a rapid synthetic route for the production of biologically interesting novel benzo[c]-
chromen-6-one molecules bearing several different substituents on benzene rings. As an application of
this methodology, several synthesized benzo[c]chromen-6-ones were transformed into highly functiona-
lized novel terphenyls.
Received 3rd September 2013,
Accepted 29th November 2013
DOI: 10.1039/c3ob41800f
www.rsc.org/obc
Introduction
Domino reactions have emerged as one of the most effective
and powerful tools for the synthesis of a range of complex
target molecules in organic and natural product synthesis.1 In
particular, they are very useful to generate a variety of new
compounds which have biological and pharmacological
activities.2
Molecules bearing benzo[c]chromen-6-one and its deriva-
tives are extensively distributed in nature (Fig. 1).3 Some of
these molecules exhibit biologically and pharmacologically
important antitumor and antibiotic activities,4 promote endo-
thelial cell proliferation, and inhibit oestrogen receptor growth
activities.5 Benzo[c]chromen-6-ones have also been used as
intermediates for the synthesis of pharmaceutically valuable
compounds, such as progesterone, androgen, and glucocorti-
coid receptor agonists.6 Furthermore, some of the known
benzo[c]chromen-6-one derivatives have promising optical pro-
perties as blue-green fluorescing dyes, which is rarer than fluo-
rescence at other wavelengths.7 In addition, benzo[c]chromen-
6-one derivatives are present in many foods, such as citrus
Fig. 1 Selected naturally occurring molecules bearing benzo[c]-
chromen-6-one moiety.
fruits, herbs, and vegetables.8 For example, autumnariol (1)
was isolated from the bulbs of Eucomis autumnalis Gerab.
(Liliaceae).9a Alternariol (2), another benzo[c]chromen-6-one
derivative, is an important metabolite of toxin-producing Alter-
naria fungi, which causes significant crop losses by fouling of
tomatoes, apples, and other fruits.9b Interestingly, alternariol
(2) has been also shown to have antiviral, antimicrobial, anti-
cancer, and cytotoxic activities.9c–e Palmariols A (3) and B (4)
were isolated from discomycete Lachnumpalmae and exhibited
antimicrobial, antinematodal, and acetylcholinesterase inhibi-
tory activities.9f,g Graphislactones A (5) and B (6) were isolated
School of Chemical Engineering, Yeungnam University, Gyeongsan 712-749, Republic
of Korea. E-mail: yrlee@yu.ac.kr; Fax: +82-53-810-4631; Tel: +82-53-810-2529
†Electronic supplementary information (ESI) available: Depiction of 1H, 13C
NMR and HRMS spectra for all products 16–45 and 49–54, and CIF data of 26.
CCDC 958927. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c3ob41800f
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from the lichen Graphisscripta var. pulverrulenta.10a–f Graphi-
slactone A (5) acts as an antioxidant and free radical scaven-
ger,11 and was found to be active against the SW1116 cell line
and an active inhibitor of AChE.10e Verrulactones A (7) and
B (8) were isolated from a culture broth of the fungal strain
Penicillium verruculosum F375,10a–f and inhibited Staphylo-
coccus aureus enoyl-ACP reductase with an IC50 of 0.92 μM and
exhibited antibacterial activity against S. aureus and MRSA
Scheme 2
derivatives via domino Michael addition/intramolecular aldol/
oxidative aromatization/lactonization reactions between substi-
tuted 2-hydroxychalcones and β-ketoesters.
with MICs of 8 μg mL−1 12
Gilvocarcins M (9) and V (10), ravi-
.
domycin (11), and chrysomycins A (12) and B (13), which have
a sugar nucleus at the C-4 position, and defucogivocarcines
M (14) and V (15), which do not bear the sugar moiety, were
isolated from other Streptomyces species found to be strong
natural anticancer agents, and to exhibit important and potent
antibacterial, antibiotic, and antitumor activities.13
We report herein a novel and efficient means for synthesiz-
ing benzo[c]chromen-6-one derivatives from readily available
substituted 2-hydroxychalcones and β-ketoesters via domino
Michael/intramolecular aldol/aromatization/lactonization reac-
tions (Scheme 2).
Given the importance of these biological and pharmacologi-
cal activities, several synthetic methods have been devised to
produce benzo[c]chromen-6-one derivatives. Of these methods,
the most useful one involves a Suzuki–Miyaura cross-coupling
reaction followed by metal or Lewis acid-mediated lactoniza-
tion of ester and methoxy groups (eqn (1), Scheme 1).14
Recently, a new reaction involving a microwave-assisted Diels–
Alder reaction between 4-cyanocoumarin and 1-oxygenated
dienes followed by elimination and aromatization with a
strong base was also described (eqn (2)).15 However, this syn-
thetic approach included two-step reactions and required puri-
fication of the intermediate. In addition, the starting materials
used for this transformation were synthesized from the corres-
ponding materials in two or more steps. Very recently, novel
one-pot reactions were devised for the synthesis of benzo[c]-
chromen-6-one derivatives by palladium bis(acetoacetonate)/
CuCl-catalyzed decarboxylative cross-coupling and lactoniza-
tion,16 or by palladium acetate-catalyzed Suzuki–Miyaura coup-
ling followed by oxidative lactonization (eqn (3) and (4)).17
However, to complete these reactions, relatively expensive cata-
lysts, reagents, and ligands are needed. Thus, a mild, general,
and efficient one-pot synthetic route for benzo[c]chromen-6-
one derivatives using inexpensive catalysts and reagents has
yet to be devised.
Results and discussion
To afford benzo[c]chromen-6-one 16, the reaction between
2-hydroxychalcone (1a) and ethyl acetoacetate (2a) was first
examined under several conditions (Table 1). Treatment of 1a
with 2a in the presence of 2 equivalents of DBU in refluxing
toluene for 7 h afforded product 16 in 50% yield, but using
sodium methoxide in refluxing methanol for 12 h, 16 was pro-
duced in 40% yield. Using K2CO3 and Cs2CO3, the desired
product 16 was produced at higher yields. For example, reac-
tion with 2 equivalents of K2CO3 in refluxing toluene for 6 h
provided product 16 in 66% yield, whereas reaction with
2 equivalents of Cs2CO3 afforded 16 in 71% yield. In recent
years, Cs2CO3 has been widely used as an excellent base for a
variety of transformations in organic synthesis.18 Importantly,
we found that Cs2CO3 is more efficient than other bases for
the production of 16 in terms of yield and reaction time.
However, using one equivalent or a catalytic amount of Cs2CO3
(0.1 eq.), the desired product was produced at lower yields.
Reactions in water or methanol under reflux conditions did
not provide the desired products. The structure of 16 was
1
determined by analyzing spectral data. The H NMR spectrum
of 16 showed a single OH peak at δ 11.30 ppm in downfield
due to hydrogen bonding with the ester carbonyl group, and
To the best of our knowledge, no previous report has been
issued on the synthesis of tricyclic benzo[c]chromen-6-one
Table 1 Reaction of 2-hydroxychalcone (1a) with ethyl acetoacetate
(2a) under several conditions
Entry
Base
Solvent
Condition
Yield (%)
1
2
3
4
5
6
7
8
DBU (2 eq.)
Toluene
MeOH
Toluene
Toluene
Toluene
Toluene
Water
Reflux, 7 h
Reflux, 12 h
Reflux, 6 h
Reflux, 2 h
Reflux, 6 h
Reflux, 12 h
Reflux, 12 h
Reflux, 12 h
50
40
66
71
55
15
0
NaOMe (2 eq.)
K2CO3 (2 eq.)
Cs2CO3 (2 eq.)
Cs2CO3 (1 eq.)
Cs2CO3 (0.1 eq.)
Cs2CO3 (2 eq.)
Cs2CO3 (2 eq.)
Scheme 1 Reported synthetic approaches for benzo[c]chromen-
6-ones.
MeOH
0
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two single peaks at δ 7.69 and 7.20 ppm associated with two
To prepare a variety of benzo[c]chromen-6-one derivatives,
aromatic peaks on the benzo[c]chromen-6-one ring. The struc- additional reactions between substituted 3-(2-hydroxyphenyl)-
ture was further confirmed by 13C NMR spectrum, which prop-2-en-1-ones and several β-ketoesters were carried out
showed the expected carbonyl peak at δ 162.6 ppm due to the under optimized reaction conditions. Results are summarized
ester. In addition, the IR spectrum of 16 contained an ester in Table 2. Reactions between 1a and ethyl-3-oxopentanoate
carbonyl absorption at 1684 cm−1
.
(2b), methyl-3-oxo-4-phenyl butanoate (2c) or diethyl-3-
Table 2 Additional reactions for the synthesis of a variety of benzo[c]chromen-6-one derivatives
Entry
1
Chalcone
β-Ketoester
Time (h)
2
Product
Yield (%)
51
2
1a
1a
2
58
3
4
5
2
2
2
60
50
70
2a
2b
2a
6
7
1c
2
3
52
55
8
1d
2c
3
63
9
2a
2b
2d
2
3
3
70
54
62
10
11
1e
1e
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Table 2 (Contd.)
Entry
Chalcone
β-Ketoester
Time (h)
2
Product
Yield (%)
72
12
13
14
2a
1f
1f
2b
2c
2
3
54
60
15
16
2a
2b
2
2
69
55
17
18
2a
2c
3
3
70
63
1i
19
20
21
2a
2b
2c
3
3
3
71
53
65
1j
1j
22
23
24
2a
2b
2d
2
2
2
73
50
64
1k
1k
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Table 2 (Contd.)
Entry
25
Chalcone
β-Ketoester
Time (h)
2
Product
Yield (%)
63
2a
26
27
1l
1l
2b
2c
3
3
51
50
28
29
2a
2c
2
2
72
61
1m
oxopentanedioate (2d) in the presence of 2 equivalents of hydroxyphenyl)prop-2-en-1-one (1m) was used, compounds 44
Cs2CO3 in refluxing toluene for 2 h provided the desired pro- and 45 were obtained in 72 and 61% yield, respectively (entries
ducts 17–19 in 51, 58, and 60% yield, respectively (entries 1–3). 28–29). These reactions provided a rapid route for synthesizing
The reaction of chalcone 1b with a methyl group on the
a
variety of benzo[c]chromen-6-one derivatives bearing
2-propen-1-one skeleton was also successful. Treatment of 1b different substituents on the benzene ring. The structures of
with 2b in the presence of Cs2CO3 in refluxing toluene for 2 h the synthesized compounds 16–45 were unambiguously con-
afforded product 20 in 50% yield (entry 4). To investigate the firmed by X-ray diffraction analysis of compound 26 (Fig. 2).
influence of substituents on reactivities, the effects of a Interestingly, the unit of the compound 26 contains two same
number of 2-hydroxychalcones (1c–1h) bearing electron-donat- molecules.
ing or -withdrawing groups on the benzene ring were next
A proposed mechanism for the Cs2CO3-mediated domino
examined. Reactions between 1c bearing a methyl group on reactions used to produce 16 is depicted in Scheme 3. In basic
the phenolic moiety and 2a or 2b afforded products 21–22 in medium, the enolate of 2a first attacks the unsaturated
70 and 52% yield, respectively, whereas those of 1d with an β-carbon to the carbonyl group of 1a to give intermediate 46,
electron-withdrawing group on the phenolic ring provided which undergoes an intramolecular aldol reaction followed by
23–24 in 55 and 63% yield, respectively (entries 5–8). Reactions
of chalcones 1e and 1f bearing electron-donating groups on
the two benzene rings were also examined. Treatment of 1e
with 2a, 2b, or 2d provided compounds 25–27 in 70, 54, and
62% yield, respectively, whereas treatment of 1f with 2a–2c
gave products 28–30 in 72, 54, and 60% yield, respectively
(entries 9–14). Reactions of chalcones 1g and 1h bearing sub-
stituents on the 1-phenyl ring with 2a or 2b gave products
31–32 in 69 and 55% yield, respectively (entries 15–16). Impor-
tantly, when (E)-3-(2-hydroxyphenyl)-1-(pyridine-3-yl)prop-2-en-
1-one (1i), (E)-3-(2-hydroxyphenyl)-1-(2,5-dimethylfuran-3-yl)-
prop-2-en-1-one
(1j),
or
(E)-3-(2-hydroxyphenyl)-1-(2,5-
dimethylthiophen-3-yl)prop-2-en-1-one (1k) were used, the
desired products 33–40 were produced in 50–73% yield
(entries 17–24). Reactions between (E)-3-(2-hydroxyphenyl)-1-
(naphthalene-2-yl)prop-2-en-1-one (1l) and β-ketoesters were
also successful. When 1l was treated with 2a, 2b, or 2c, pro-
ducts 41–43 were produced in 63, 51, and 50% yield, respect-
Fig. 2 X-ray structure of compound 26 containing two molecules in a
ively
(entries
25–27).
When
(E)-1-cyclopropyl-3-(2-
unit.
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reported for the synthesis of terphenyls, synthetic methods are
still required for the production of polysubstituted terphenyls.
The conversions of several synthesized benzo[c]chromen-6-
ones into substituted terphenyls were also attempted, as
shown in Table 3. Treatment of 20 with methyl iodide in the
presence of KOH in wet DMSO at room temperature for 2 h
provided 49 in 70% yield. Similarly, reactions of 23, 30, 39, 42,
and 45 with methyl iodide also provided the desired polysub-
stituted terphenyls 50–54 in 78–87% yield. Importantly, these
reactions rapidly provided various terphenyls bearing substitu-
ents, such as, –Br, –Me, –COOMe, –OMe, aryl, cyclopropyl, and
furyl on their benzene rings.
Scheme 3 Proposed mechanism for the formation of 7-hydroxy-9-
phenyl-6H-benzo[c]chromen-6-one (16) via domino reactions.
oxidative aromatization to form intermediate 48. Finally, the
lactonization of 48 under basic conditions results in 16.
As an example of this methodology, several synthesized
benzo[c]chromen-6-ones were converted into biologically and
physically interesting polysubstituted terphenyls. Molecules
bearing the terphenyl moiety are found in a variety of natural
products19 and exhibit a number of potent biological pro-
perties, which include antioxidant, neuroprotective, cytotoxic,
antithrombotic, and anticoagulant activities.20 In addition,
these molecules play a significant role in the fields of optical
materials, liquid crystals, spacers in catenane, and porphyrin
chemistry.21 Because of their important biological and physi-
cal properties, a number of synthetic methods have been
devised to produce terphenyls.22 These reactions typically
included aryl zinc reagents with functionalized biphenyl nona-
flates,23 Grignard reagents containing dihalobenzenes, and
triazene-substituted arylboronic esters.24 Recently, other meth-
odologies using Suzuki cross-coupling reactions between di-
halobenzenes and arylboronic acids,25 the gold-catalyzed
cycloaromatization of dienynes,26 DMEDA-catalyzed direct
C–H arylation of unactivated benzenes,27 and rhodium-cata-
Conclusions
We described the Cs2CO3-promoted one-pot synthesis of bio-
logically interesting benzo[c]chromen-6-one derivatives starting
from substituted 2-hydroxychalcones and β-ketoesters. These
reactions were accomplished by domino Michael addition/
intramolecular aldol/oxidative aromatization/lactonization.
The described methodology has the advantages of requiring
mild reaction conditions and inexpensive non-transition
metals and domino one-pot reactions. In particular, the syn-
thesized molecules were readily converted under basic con-
ditions into biologically interesting novel terphenyls bearing
different substituents on their benzene rings.
Experimental
All experiments were carried out under open air without using
any inert gas protection. β-Ketoesters (2a–d) were purchased
lyzed formal [2 + 2 + 2] cycloaddition reactions of alkynes have from Sigma-Aldrich. Merck precoated silica gel plates (Art.
been described.28 Although a number of methods have been
5554) with a fluorescent indicator were used for analytical
Table 3 Conversion of benzo[c]chromen-6-ones to polysubstituted terphenyls 49–54
Benzo[c]chromen-6-one Time (h) Product
Yield (%) Benzo[c]chromen-6-one Time (h) Product
Yield (%)
87
20
23
30
2
1
2
70
85
85
39
42
42
1
1
1
78
86
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TLC. Flash column chromatography was performed using
7-Hydroxy-8,9-diphenyl-6H-benzo[c]chromen-6-one
(18).
silica gel 9385 (Merck). Melting points were determined with Reaction of 1a (224 mg, 1.0 mmol) and β-ketoester 2c (288 mg,
micro-cover glasses on a Fisher-Johns apparatus and are uncor- 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) afforded 18
1
rected. 1H NMR spectra were recorded on a Varian-VNS (211 mg, 58%) as a solid: mp 213–215 °C; H NMR (300 MHz,
(300 MHz) spectrometer in CDCl3 using 7.24 ppm as the CDCl3) δ 11.77 (1H, s), 8.00 (1H, d, J = 7.5 Hz), 7.60 (1H, s),
solvent chemical shift. 13C NMR spectra were recorded on a 7.47–7.31 (3H, m), 7.21–7.19 (6H, m), 7.16–7.13 (4H, m); 13C
Varian-VNS (75 MHz) spectrometer in CDCl3 using 77.0 ppm NMR (75 MHz, CDCl3) δ 165.6, 160.0, 150.5, 150.3, 140.2,
as the solvent chemical shift. IR spectra were recorded on a 134.8, 133.6, 131.0, 130.5, 129.4, 128.4, 127.9, 127.7, 127.5,
JASCO FTIR 5300 spectrophotometer. High resolution mass 127.1, 125.1, 123.1, 118.1, 117.6, 114.0, 104.8; IR (KBr) 3448,
(HRMS) were obtained with a JEOL JMS-700 spectrometer at 3063, 1674, 1612, 1396, 1265, 1127, 752, 697 cm−1; HRMS m/z
the Korea Basic Science Institute.
(M+) calcd for C25H16O3: 364.1099. Found: 364.1098.
Ethyl-7-hydroxy-6-oxo-9-phenyl-6H-benzo[c]chromene-8-car-
boxylate (19). Reaction of 1a (224 mg, 1.0 mmol) and β-keto-
ester 2d (303 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol)
afforded 19 (216 mg, 60%) as a solid: mp 193–195 °C; 1H NMR
(300 MHz, CDCl3) δ 11.67 (1H, s), 7.84 (1H, d, J = 7.5 Hz),
7.36–7.35 (7H, m), 7.24–7.17 (2H, m), 4.07 (2H, q, J = 7.2 Hz),
0.938 (3H, t, J = 7.2 Hz); 13C NMR (75 MHz, CDCl3) δ 165.9,
164.7, 159.5, 150.5, 148.9, 139.0, 135.5, 131.2, 128.6, 128.4,
127.8, 125.2, 123.2, 121.4, 117.5, 117.2, 113.1, 104.3, 61.3, 13.5;
General procedure for the synthesis of 2-hydroxychalcones
(1a–m)
To a solution of ketones (20.0 mmol) in ethanol (50 mL) were
added KOH (5.6 g, 100.0 mmol) and salicylaldehydes
(20.0 mmol) at room temperature. The reaction mixture was
stirred at room temperature for 48 h. Evaporation of ethanol,
addition of water (50 ml) and 1 N HCl (50 mL), extraction with
EtOAc (3 × 50 mL), washing with brine (50 mL), and removal of
the solvent followed by flash column chromatography on silica
gel using hexane–EtOAc (10 : 1) gave 2-hydroxychalcones
(1a–1m) in the range of 53–84% yield.
IR (KBr) 3455, 3106, 1737, 1552, 1127, 1015, 858, 742 cm−1
;
HRMS m/z (M+) calcd for C22H16O5: 360.0998. Found:
360.0994.
7-Hydroxy-8,10-dimethyl-9-phenyl-6H-benzo[c]chromen-6-one
(20). Reaction of 1b (238 mg, 1.0 mmol) and β-ketoester 2b
(216 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol)
afforded 20 (158 mg, 50%) as a solid: mp 207–209 °C; 1H NMR
General procedure for the synthesis of benzo[c]chromen-
6-ones (16–45)
To
a solution of 2-hydroxychalcone compounds 1a–1m (300 MHz, CDCl3) δ 12.07 (1H, s), 8.18 (1H, d, J = 8.1 Hz),
(1.0 mmol) and β-ketoesters 2a–2d (1.5 mmol) in toluene 7.50–7.37 (5H, m), 7.29 (1H, t, J = 7.2 Hz), 7.14 (2H, d, J = 7.2
(4 mL) was added Cs2CO3 (2.0 mmol). The reaction mixture Hz), 2.36 (3H, s), 1.98 (3H, s); 13C NMR (75 MHz, CDCl3) δ
was refluxed in open air for 2 h. Then the solvent was evapor- 166.4, 158.9, 153.1, 150.4, 140.6, 129.2, 128.8, 128.3, 127.8,
ated in a rotary evaporator under reduced pressure to give the 127.8, 127.4, 125.1, 124.1, 123.3, 120.2, 117.5, 105.3, 22.0, 13.9;
residue. The residue was purified by flash column chromato- IR (KBr) 3437, 3067, 1685, 1616, 1272, 1124, 758 cm−1; HRMS
graphy on silica gel to give the products. Characterization data m/z (M+) calcd for C21H16O3: 316.1099. Found: 316.1099.
for all compounds 16–45 are as follows.
7-Hydroxy-2-methyl-9-phenyl-6H-benzo[c]chromen-6-one (21).
7-Hydroxy-9-phenyl-6H-benzo[c]chromen-6-one (16). Reac- Reaction of 1c (238 mg, 1.0 mmol) and β-ketoester 2a (195 mg,
tion of 1a (224 mg, 1.0 mmol) and β-ketoester 2a (195 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) afforded 21
1
1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) afforded 16 (211 mg, 70%) as a solid: mp 198–200 °C; H NMR (300 MHz,
1
(204 mg, 71%) as a solid: mp 213–215 °C; H NMR (300 MHz, CDCl3) δ 11.27 (1H, s), 7.66 (1H, s), 7.57–7.54 (3H, m),
CDCl3) δ 11.30 (1H, s), 8.02 (1H, d, J = 7.8 Hz), 7.68 (1H, s), 7.42–7.34 (3H, m), 7.15–7.06 (3H, m), 2.33 (3H, s); 13C NMR
7.60 (2H, d, J = 6.9 Hz), 7.44–7.36 (4H, m), 7.31–7.27 (2H, m), (75 MHz, CDCl3) δ 165.3, 162.5, 149.9, 148.7, 139.4, 135.3,
7.20 (1H, s); 13C NMR (75 MHz, CDCl3) δ 162.6, 162.3, 150.7, 134.7, 131.5, 128.9, 128.9, 127.3, 123.0, 117.7, 117.3, 114.6,
150.2, 139.4, 135.4, 130.7, 129.1, 129.0, 127.4, 125.1, 123.3, 110.7, 104.7, 21.0; IR (KBr) 3434, 3033, 1680, 1560, 1227, 1211,
118.3, 117.8, 114.9, 111.1, 104.8; IR (KBr) 3422, 3036, 2367, 1096, 758, 696 cm−1; HRMS m/z (M+) calcd for C20H14O3:
1684, 1620, 1276, 1083, 757 cm−1; HRMS m/z (M+) calcd for 302.0943. Found: 302.0945.
C19H12O3: 288.0786. Found: 288.0788.
7-Hydroxy-2,8-dimethyl-9-phenyl-6H-benzo[c]chromen-6-one
7-Hydroxy-8-methyl-9-phenyl-6H-benzo[c]chromen-6-one (17). (22). Reaction of 1c (238 mg, 1.0 mmol) and β-ketoester 2b
Reaction of 1a (224 mg, 1.0 mmol) and β-ketoester 2b (216 mg, (216 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol)
1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) afforded 17 afforded 22 (164 mg, 52%) as a solid: mp 193–195 °C; 1H NMR
1
(154 mg, 51%) as a solid: mp 166–168 °C; H NMR (300 MHz, (300 MHz, CDCl3) δ 11.66 (1H, s), 7.61 (1H, s), 7.41–7.33 (3H,
CDCl3) δ 11.76 (1H, s), 7.99 (1H, d, J = 8.1 Hz), 7.51–7.28 (9H, m), 7.31–7.26 (3H, m), 7.10–7.06 (2H, m), 2.29 (3H, s), 2.11
m), 2.25 (3H, s); 13C NMR (75 MHz, CDCl3) δ 165.6, 160.7, (3H, s); 13C NMR (75 MHz, CDCl3) δ 165.7, 160.7, 150.8, 148.4,
151.0, 150.4, 140.6, 131.6, 130.3, 128.7, 128.3, 127.8, 124.9, 140.6, 134.6, 131.6, 130.9, 128.7, 128.3, 127.8, 123.6, 122.8,
123.9, 122.9, 118.4, 117.5, 113.3, 104.1, 13.0; IR (KBr) 3449, 117.9, 117.1, 113.1, 104.1, 21.0, 13.0; IR (KBr) 3456, 2932,
3062, 2370, 1677, 1268, 1125, 754 cm−1; HRMS m/z (M+) calcd 1688, 1602, 1513, 1375, 1190, 1014, 821, 745 cm−1; HRMS m/z
for C20H14O3: 302.0943. Found: 302.0943.
(M+) calcd for C21H16O3: 316.1099. Found: 316.1097.
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2-Bromo-7-hydroxy-8-methyl-9-phenyl-6H-benzo[c]chromen- 824 cm−1; HRMS m/z (M+) calcd for C24H20O5: 388.1311.
6-one (23). Reaction of 1d (301 mg, 1.0 mmol) and β-ketoester Found: 388.1313.
2b (216 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol)
7-Hydroxy-3-methoxy-9-(3-methoxyphenyl)-6H-benzo[c]-
afforded 23 (209 mg, 55%) as a solid: mp 216–218 °C; 1H NMR chromen-6-one (28). Reaction of 1f (284 mg, 1.0 mmol) and
(300 MHz, CDCl3) δ 11.59 (1H, s), 8.02 (1H, s), 7.50–7.39 (4H, β-ketoester 2a (195 mg, 1.5 mmol) using Cs2CO3 (650 mg,
m), 7.36–7.32 (3H, m), 7.17 (1H, d, J = 8.7 Hz), 2.20 (3H, s); 13
C
2.0 mmol) afforded 28 (250 mg, 72%) as a solid: mp
NMR (75 MHz, CDCl3) δ 165.1, 160.8, 151.2, 149.2, 140.3, 190–192 °C; 1H NMR (300 MHz, CDCl3) δ 11.26 (1H, s), 7.92
132.8, 130.2, 128.7, 128.4, 128.0, 125.7, 125.0, 120.2, 119.2, (1H, d, J = 8.7 Hz), 7.57 (1H, s), 7.35 (1H, t, J = 7.8 Hz),
118.0, 113.5, 103.9, 13.1; IR (KBr) 3449, 3064, 1703, 1625, 1557, 7.20–7.18 (2H, m), 7.13–7.12 (1H, m), 6.94–6.80 (3H, m), 3.82
1409, 1264, 1217, 1082, 853, 691 cm−1; HRMS m/z (M+) calcd (6H, s); 13C NMR (75 MHz, CDCl3) δ 165.8, 162.1, 160.5, 159.4,
for C20H13BrO3: 380.0048. Found: 380.0050.
151.6, 150.9, 142.1, 132.1, 129.3, 123.9, 122.5, 121.1, 114.5,
2-Bromo-7-hydroxy-8,9-diphenyl-6H-benzo[c]chromen-6-one 113.1, 112.8, 112.5, 111.4, 103.3, 101.4, 55.6, 55.3; IR (KBr)
(24). Reaction of 1d (301 mg, 1.0 mmol) and β-ketoester 2c 3449, 2930, 1679, 1632, 1623, 1464, 1396, 1266, 1092, 1029,
(288 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) 800, 725 cm−1; HRMS m/z (M+) calcd for C21H16O5: 348.0998.
afforded 24 (243 mg, 63%) as a solid: mp 215–217 °C; 1H NMR Found: 348.0999.
(300 MHz, CDCl3) δ 11.67 (1H, s), 8.12 (1H, s), 7.55–7.53 (2H,
7-Hydroxy-3-methoxy-9-(3-methoxyphenyl)-8-methyl-6H-benzo-
m), 7.22–7.19 (7H, m), 7.14–7.09 (4H, m); 13C NMR (75 MHz, [c]chromen-6-one (29). Reaction of 1f (284 mg, 1.0 mmol) and
CDCl3) δ 165.1, 160.2, 150.7, 149.5, 140.0, 134.6, 133.3, 132.3, β-ketoester 2b (216 mg, 1.5 mmol) using Cs2CO3 (650 mg,
130.9, 129.4, 129.3, 128.0, 127.8, 127.6, 127.2, 126.0, 120.0, 2.0 mmol) afforded 29 (153 mg, 54%) as a solid: mp
119.4, 118.2, 114.2, 104.7; IR (KBr) 3454, 3064, 1681, 1612, 171–173 °C; 1H NMR (300 MHz, CDCl3) δ 11.57 (1H, s), 7.75
1545, 1393, 1260, 1203, 1115, 880, 743, 701 cm−1; HRMS m/z (1H, d, J = 8.7 Hz), 7.32–7.24 (2H, m), 6.89–6.72 (5H, m), 3.78
(M+) calcd for C25H15BrO3: 442.0205. Found: 442.0202.
(3H, s), 3.77 (3H, s), 2.11 (3H, s); 13C NMR (75 MHz, CDCl3)
7-Hydroxy-2-methyl-9-p-tolyl-6H-benzo[c]chromen-6-one (25). δ 165.9, 161.1, 160.6, 159.4, 151.6, 150.9, 142.1, 132.1, 129.3,
Reaction of 1e (252 mg, 1.0 mmol) and β-ketoester 2a (195 mg, 123.9, 122.5, 121.1, 114.5, 113.1, 112.8, 112.5, 111.4, 103.3,
1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) afforded 25 101.4, 55.6, 55.3, 12.9; IR (KBr) 3448, 2929, 1672, 1622, 1482,
1
(221 mg, 70%) as a solid: mp 258–260 °C; H NMR (300 MHz, 1282, 1137, 1033, 798, 751 cm−1; HRMS m/z (M+) calcd for
CDCl3 δ 11.40 (1H, s), 7.85 (1H, s), 7.72 (1H, s), 7.58 (2H, d, J = C22H18O5: 362.1154. Found: 362.1154.
7.5 Hz), 7.31–7.24 (5H, m), 2.45 (3H, s), 2.42 (3H, s); 13C NMR
7-Hydroxy-3-methoxy-9-(3-methoxyphenyl)-8-phenyl-6H-benzo-
(75 MHz, CDCl3) δ 165.7, 160.7, 151.0, 150.4, 137.7, 137.7, [c]chromen-6-one (30). Reaction of 1f (284 mg, 1.0 mmol) and
131.6, 129.9, 129.0, 128.7, 124.9, 123.9, 122.9, 118.5, 117.5, β-ketoester 2c (288 mg, 1.5 mmol) using Cs2CO3 (650 mg,
113.4, 104.0, 21.2, 13.1; IR (KBr) 3434, 2928, 1690, 1618, 1588, 2.0 mmol) afforded 30 (254 mg, 60%) as a solid: mp
1437, 1240, 1181, 1076, 926, 784 cm−1; HRMS m/z (M+) calcd 216–218 °C; 1H NMR (300 MHz, CDCl3) δ 11.69 (1H, s), 7.87
for C21H16O3: 316.1099. Found: 316.1102.
(1H, d, J = 9.0 Hz), 7.47 (1H, s), 7.24–7.06 (6H, m), 6.88–6.80
7-Hydroxy-2,8-dimethyl-9-p-tolyl-6H-benzo[c]chromen-6-one (2H, m), 6.73–6.88 (2H, m), 6.56 (1H, s) 3.82 (3H, s), 3.52 (3H,
(26). Reaction of 1e (252 mg, 1.0 mmol) and β-ketoester 2b s); 13C NMR (75 MHz, CDCl3) δ 165.8, 161.7, 161.6, 160.0,
(216 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) 158.9, 151.9, 150.2, 141.6, 135.0, 134.2, 130.9, 129.0, 127.8,
afforded 26 (178 mg, 54%) as a solid: mp 190–192 °C; 1H NMR 127.1, 124.2, 121.8, 114.8, 113.5, 113.1, 111.1, 104.0, 101.4,
(300 MHz, CDCl3) δ 11.64 (1H, s), 7.59 (1H, s), 7.2 (1H, s), 55.7, 55.1; IR (KBr) 3444, 2935, 1679, 1639, 1464, 1396, 1266,
7.21–7.15 (4H, m), 7.11–7.04 (2H, m), 2.35 (3H, s), 2.28 (3H, s), 1092, 1029, 805, 735 cm−1; HRMS m/z (M+) calcd for C27H20O5:
2.11 (3H, s); 13C NMR (75 MHz, CDCl3) δ 165.7, 160.6, 150.8, 424.1311. Found: 424.1309.
148.4, 137.7, 137.6, 134.5, 131.5, 130.8, 128.9, 128.6, 123.6,
122.8, 117.9, 117.1, 113.2, 103.9, 21.2, 21.0, 13.0; IR (KBr) tion of 1g (238 mg, 1.0 mmol) and β-ketoester 2a (195 mg,
3442, 3056, 1672, 1610, 1398, 1270, 1136, 1019, 862, 761 cm−1
1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) afforded 31
HRMS m/z (M+) calcd for C22H18O3: 330.1256. Found: (208 mg, 69%) as a solid: mp 199–201 °C; H NMR (300 MHz,
7-Hydroxy-9-p-tolyl-6H-benzo[c]chromen-6-one
(31). Reac-
;
1
330.1256.
Ethyl
CDCl3) δ 11.34 (1H, s), 8.07 (2H, d, J = 7.2 Hz), 7.73 (1H, s),
7-hydroxy-2-methyl-6-oxo-9-p-tolyl-6H-benzo[c]chro- 7.50–7.45 (2H, m), 7.37–7.25 (5H, m), 2.41 (3H, s); 13C NMR
mene-8-carboxylate (27). Reaction of 1e (252 mg, 1.0 mmol) (75 MHz, CDCl3) δ 165.3, 162.5, 150.7, 150.2, 139.1, 136.5,
and β-ketoester 2d (303 mg, 1.5 mmol) using Cs2CO3 (650 mg, 135.3, 130.6, 129.7, 127.2, 125.0, 123.3, 118.4, 117.7, 114.6,
2.0 mmol) afforded 27 (240 mg, 62%) as a solid: mp 110.8, 104, 12.2; IR (KBr) 3436, 3128, 1686, 1623, 1273, 1110,
223–225 °C; 1H NMR (300 MHz, CDCl3) δ 11.78 (1H, s), 7.73 944, 813, 752, 705 cm−1; HRMS m/z (M+) calcd for C20H14O3:
(1H, s), 7.46 (1H, s), 7.32–7.17 (6H, m), 4.12 (2H, q, J = 7.2 Hz), 302.0943. Found: 302.0946.
2.37 (3H, s), 2.34 (3H, s), 1.01 (3H, t, J = 7.2 Hz); 13C NMR
7-Hydroxy-9-(4-methoxyphenyl)-8-methyl-6H-benzo[c]chromen-
(75 MHz, CDCl3) δ 166.3, 165.2, 159.8, 149.1, 149.0, 138.7, 6-one (32). Reaction of 1h (254 mg, 1.0 mmol) and β-ketoester
136.4, 135.8, 135.0, 132.2, 129.2, 128.0, 123.4, 121.6, 117.5, 2b (216 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol)
117.3, 113.3, 104.8, 61.5, 21.2, 21.0, 13.7; IR (KBr) 3438, 2989, afforded 32 (182 mg, 55%) as a solid: mp 192–194 °C; 1H NMR
2733, 1732, 1671, 1552, 1405, 1248, 1205, 1133, 1021, (300 MHz, CDCl3) δ 11.62 (1H, s), 7.87 (1H, d, J = 7.8 Hz)),
926 | Org. Biomol. Chem., 2014, 12, 919–930
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7.36–7.31 (2H, m), 7.24–7.17 (4H, m), 6.92 (2H, d, J = 8.4 Hz), β-ketoester 2c (288 mg, 1.5 mmol) using Cs2CO3 (650 mg,
3.80 (3H, s), 2.14 (3H, s); 13C NMR (75 MHz, CDCl3) δ 165.6, 2.0 mmol) afforded 37 (248 mg, 65%) as a solid: mp
160.7, 159.3, 150.6, 150.3, 132.8, 131.5, 130.0, 129.9, 124.9, 208–210 °C; 1H NMR (300 MHz, CDCl3) δ 11.71 (1H, s), 7.96
123.9, 122.9, 118.4, 117.5, 113.7, 113.4, 103.8, 55.3, 13.1; (1H, d, J = 7.8 Hz), 7.49 (1H, s), 7.43 (1H, t, J = 7.8 Hz),
IR (KBr) 3453, 3073, 1675, 1612, 1510, 1274, 1129, 1029, 834, 7.33–7.18 (7H, m), 5.51 (1H, s), 2.08 (3H, s), 1.92 (3H, s); 13C
736 cm−1; HRMS m/z (M+) calcd for C21H16O4: 332.1049. NMR (75 MHz, CDCl3) δ 165.6, 160.1, 150.6, 149.6, 147.2,
Found: 332.1050.
143.5, 135.1, 133.4, 130.6, 130.5, 127.8, 127.2, 125.1, 123.0,
7-Hydroxy-9-(pyridin-3-yl)-6H-benzo[c]chromen-6-one (33). 120.6, 118.2, 117.7, 114.1, 108.2, 105.4, 104.5, 13.2, 12.5; IR
Reaction of 1i (225 mg, 1.0 mmol) and β-ketoester 2a (195 mg, (KBr) 3444, 3067, 1680, 1624, 1272, 1124, 759 cm−1; HRMS m/z
1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) afforded 33 (M+) calcd for C25H18O4: 382.1205. Found: 382.1208.
1
(220 mg, 70%) as a solid: mp 243–245 °C; H NMR (300 MHz,
2-Bromo-9-(2,5-dimethylthiophen-3-yl)-7-hydroxy-6H-benzo[c]-
CDCl3) δ 11.41 (1H, s), 8.93 (1H, s), 8.69 (1H, s), 8.07 (1H, d, J = chromen-6-one (38). Reaction of 1k (337 mg, 1.0 mmol) and
8.1 Hz), 7.97 (1H, d, J = 7.5 Hz), 7.72 (1H, s), 7.52–7.36 (4H, m), β-ketoester 2a (195 mg, 1.5 mmol) using Cs2CO3 (650 mg,
7.22 (1H, s); 13C NMR (75 MHz, CDCl3) δ 164.6, 162.6, 150.5, 2.0 mmol) afforded 38 (292 mg, 73%) as a solid: mp
149.5, 149.5, 139.0, 133.9, 133.4, 129.2, 129.1, 127.3, 126.0, 217–219 °C; 1H NMR (300 MHz, CDCl3) δ 11.16 (1H, s), 8.03
120.1, 119.4, 118.1, 115.6, 111.1, 104.6; IR (KBr) 3425, 3043, (1H, s), 7.49 (1H, d, J = 8.7 Hz), 7.39 (1H, s), 7.16 (1H, d, J =
1685, 1621, 1276, 1207, 1086, 754, 707 cm−1; HRMS m/z (M+) 8.7 Hz), 7.01 (1H, s), 6.70 (1H, s), 2.43 (3H, s), 2.39 (3H, s); 13C
calcd for C18H11NO3: 289.0739. Found: 289.0741.
NMR (75 MHz, CDCl3) δ 164.6, 162.4, 149.6, 146.4, 136.7,
7-Hydroxy-8-phenyl-9-(pyridin-3-yl)-6H-benzo[c]chromen-6- 136.3, 134.6, 133.6, 133.4, 126.4, 126.0, 120.2, 119.5, 118.1,
one (34). Reaction of 1i (225 mg, 1.0 mmol) and β-ketoester 2c 116.9 112.6, 104.0, 15.0, 14.3; IR (KBr) 3451, 2377, 1677, 1390,
(288 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) 1268, 756 cm−1; HRMS m/z (M+) calcd for C19H13BrO3S:
afforded 34 (229 mg, 63%) as a solid: mp 247–249 °C; 1H NMR 399.9769. Found: 399.9771.
(300 MHz, CDCl3) δ 11.82 (1H, s), 8.48 (2H, d, J = 7.8 Hz), 8.03
2-Bromo-9-(2,5-dimethylthiophen-3-yl)-7-hydroxy-8-methyl-
(1H, d, J = 8.1 Hz), 7.59 (1H, s), 7.49 (1H, t, J = 6.9 Hz), 6H-benzo[c]chromen-6-one (39). Reaction of 1k (337 mg,
7.40–7.35 (3H, m), 7.23–7.24 (3H, m), 7.14–7.12 (3H, m); 13C 1.0 mmol) and β-ketoester 2b (216 mg, 1.5 mmol) using
NMR (75 MHz, CDCl3) δ 165.4, 160.2, 150.6, 149.4, 148.3, Cs2CO3 (650 mg, 2.0 mmol) afforded 39 (207 mg, 73%) as a
1
146.3, 137.0, 136.2, 134.1, 134.0, 131.0, 130.9, 128.7, 128.1, solid: mp 213–215 °C; H NMR (300 MHz, CDCl3) δ 11.63 (1H,
127.5, 125.3, 123.1, 122.7, 117.8, 117.7, 113.6, 105.5; IR (KBr) s), 8.09 (1H, s), 7.54 (1H, d, J = 9.0 Hz), 7.36 (1H, s), 7.25 (1H,
3443, 3056, 1663, 1610, 1391, 1264, 1129, 748 cm−1; HRMS m/z d, J = 8.7 Hz), 6.56 (1H, s), 2.50 (3H, s), 2.24 (3H, s), 2.19 (3H,
(M+) calcd for C24H15NO3: 365.1052. Found: 365.1049.
s); 13C NMR (75 MHz, CDCl3) δ 165.2, 160.8, 149.3, 146.7,
9-(2,5-Dimethylfuran-3-yl)-7-hydroxy-6H-benzo[c]chromen- 136.7, 136.5, 133.4, 132.8, 130.1, 126.6, 126.2, 125.8, 120.3,
6-one (35). Reaction of 1j (242 mg, 1.0 mmol) and β-ketoester 119.3, 118.0, 113.7, 104.0, 15.1, 13.6, 12.9; IR (KBr) 3477, 1689,
2a (195 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) 1551, 1388, 1259, 1122, 734 cm−1; HRMS m/z (M+) calcd for
afforded 35 (217 mg, 71%) as a solid: mp 141–143 °C; 1H NMR C20H15BrO3S: 413.9925. Found: 413.9927.
(300 MHz, CDCl3) δ 11.29 (1H, s), 7.95 (1H, d, J = 8.7 Hz),
Ethyl
2-bromo-9-(2,5-dimethylthiophen-3-yl)-7-hydroxy-
7.47–7.41 (2H, m), 7.33–7.28 (2H, m), 7.00 (1H, s), 6.17 (1H, s), 6-oxo-6H-benzo[c]chromene-8-carboxylate (40). Reaction of 1k
2.47 (3H, s), 2.29 (3H, s); 13C NMR (75 MHz, CDCl3) δ 165.1, (337 mg, 1.0 mmol) and β-ketoester 2d (216 mg, 1.5 mmol)
162.3, 150.6, 150.5, 148.1, 143.8, 135.0, 130.5, 124.9, 123.1, using Cs2CO3 (650 mg, 2.0 mmol) afforded 40 (207 mg, 64%)
1
120.5, 118.2, 117.7, 114.4, 110.7, 106.2, 103.7, 13.5, 13.3; IR as a solid: mp 203–205 °C; H NMR (300 MHz, CDCl3) δ 11.68
(KBr) 3449, 2930, 1719, 1511, 1278, 1128, 817, 557 cm−1
;
(1H, s), 8.1 (1H, s), 7.6 (1H, d, J = 7.6 Hz), 7.39 (1H, s), 7.26
HRMS m/z (M+) calcd for C19H14O4: 306.0892. Found: (1H, d, J = 8.7 Hz), 6.57 (1H, s), 4.15 (2H, q, J = 7.2 Hz), 2.41
306.0890.
(3H, s), 2.29 (3H, s), 1.09 (3H, t, J = 7.2 Hz); 13C NMR (75 MHz,
9-(2,5-Dimethylfuran-3-yl)-7-hydroxy-8-methyl-6H-benzo[c]- CDCl3) δ 165.6, 164.4, 159.7, 149.8, 145.3, 136.5, 135.0, 134.4,
chromen-6-one (36). Reaction of 1j (242 mg, 1.0 mmol) and 134.2, 134.1, 126.4, 126.3, 123.5, 119.6, 119.5, 118.4, 114.1,
β-ketoester 2b (216 mg, 1.5 mmol) using Cs2CO3 (650 mg, 104.9, 61.5, 15.0, 13.8, 13.7; IR (KBr) 3477, 1689, 1551, 1388,
2.0 mmol) afforded 36 (169 mg, 53%) as a solid: mp 1259, 1122, 734 cm−1; HRMS m/z (M+) calcd for C22H17BrO5S:
144–146 °C; 1H NMR (300 MHz, CDCl3) δ 11.61 (1H, s), 7.89 471.9980. Found: 471.9982.
(1H, d, J = 7.8 Hz), 7.39–7.34 (2H, m), 7.27–7.17 (2H, m), 5.93
7-Hydroxy-9-(naphthalen-2-yl)-6H-benzo[c]chromen-6-one
(1H, s), 2.25 (3H, s), 2.16 (6H, s); 13C NMR (75 MHz, CDCl3) δ (41). Reaction of 1l (274 mg, 1.0 mmol) and β-ketoester 2a
165.7, 160.7, 150.4, 150.0, 147.0, 143.8, 131.5, 130.0, 125.0, (195 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol)
124.9, 122.9, 120.6, 118.5, 117.6, 113.6, 108.1, 103.9, 13.4, 13.0, afforded 41 (212 mg, 63%) as a solid: mp 228–230 °C; 1H NMR
12.5; IR (KBr) 3449, 3067, 1686, 1624, 1272, 1124, 757 cm−1
;
(300 MHz, CDCl3) δ 11.40 (1H, s), 8.14 (2H, d, J = 6.9 Hz),
HRMS m/z (M+) calcd for C20H16O4: 320.1049. Found: 7.97–7.88 (4H, m), 7.78 (1H, d, J = 8.1 Hz), 7.55–7.48 (3H, m),
320.1046.
7.39–7.35 (3H, m); 13C NMR (75 MHz, CDCl3) δ 165.9, 161.8,
9-(2,5-Dimethylfuran-3-yl)-7-hydroxy-8-phenyl-6H-benzo[c]- 152.0, 150.8, 138.1, 133.1, 133.7, 131.7, 131.0, 128.2, 127.9,
chromen-6-one (37). Reaction of 1j (242 mg, 1.0 mmol) and 127.8, 127.7, 126.7, 126.5, 126.4, 125.0, 124.5, 123.0, 118.4,
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117.9, 113.5, 104.8; IR (KBr) 3422, 2370, 1683, 1620, 1557, room temperature for 1–2 h (progress of reaction was moni-
1272, 1081, 858, 755 cm−1; HRMS m/z (M+) calcd for C23H14O3: tored by thin layer chromatography). The reaction mixture was
338.0943. Found: 338.0943.
extracted with ethyl acetate and evaporated in a rotary evapor-
7-Hydroxy-8-methyl-9-(naphthalen-2-yl)-6H-benzo[c]chromen- ator under reduced pressure. The residue was purified by flash
6-one (42). Reaction of 1l (274 mg, 1.0 mmol) and β-ketoester column chromatography on silica gel to give the products.
2b (195 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) Characterization data for all synthesized terphenyls 49–54 are
afforded 42 (179 mg, 51%) as a solid: mp 194–196 °C; 1H NMR as follows.
(300 MHz, CDCl3) δ 11.68 (1H, s), 7.90–7.79 (4H, m), 7.74 (1H,
Methyl 2″,5′-dimethoxy-2′,6′-dimethyl-[1,1′:3′,1″-terphenyl]-
s), 7.47–7.44 (3H, m), 7.41–7.33 (2H, m), 7.27–7.16 (2H, m), 4′-carboxylate (49). Reaction of 20 (126 mg, 0.4 mmol) and
2.17 (3H, s); 13C NMR (75 MHz, CDCl3) δ 165.7, 160.8, 151.0, methyl iodide (284 mg, 2.0 mmol) using KOH (112 mg,
150.5, 138.1, 133.1, 132.7, 131.7, 130.0, 128.12, 127.9, 127.8, 2.0 mmol) afforded 49 (105 mg, 70%) as a solid: mp
127.7, 126.7, 126.5, 126.4, 125.0, 124.1, 123.0, 118.4, 117.6, 99–101 °C; 1H NMR (300 MHz, CDCl3) δ 7.45–7.39 (2H, m),
113.5, 104.3, 13.2; IR (KBr) 3447, 3053, 1676, 1268, 1123, 7.35–7.26 (2H, m), 7.20–7.17 (1H, m), 7.13–7.09 (2H, m),
755 cm−1; HRMS m/z (M+) calcd for C24H16O3: 352.1099. 6.96–6.90 (2H, m), 3.82 (3H, s), 3.76 (3H, s), 3.48 (3H, s), 1.97
Found: 352.1097.
(3H, s), 1.66 (3H, s); 13C NMR (75 MHz, CDCl3) δ 168.4, 156.9,
7-Hydroxy-9-(naphthalen-2-yl)-8-phenyl-6H-benzo[c]chromen- 152.7, 144.6, 140.9, 134.6, 132.2, 131.2, 130.8, 128.9, 128.4,
6-one (43). Reaction of 1l (274 mg, 1.0 mmol) and β-ketoester 128.1, 128.0, 126.8, 126.3, 120.2, 110.6, 62.1, 56.3, 51.6, 17.9,
2c (288 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) 14.0; IR (KBr) 3048, 1680, 1612, 1548, 1405, 1273, 1163,
afforded 43 (207 mg, 50%) as a solid: mp 199–201 °C; 1H NMR 768 cm−1; HRMS m/z (M+) calcd for C24H24O4: 376.1675.
(300 MHz, CDCl3) δ 11.84 (1H, s), 8.09 (1H, d, J = 7.2 Hz), Found: 376.1677.
7.76–7.47 (4H, m), 7.6 (1H, d, J = 8.4 Hz), 7.53–7.33 (5H, m),
Methyl 5″-bromo-2″,5′-dimethoxy-6′-methyl-[1,1′:3′,1″-terphe-
7.22–7.18 (5H, m), 7.15–7.12 (1H, m); 13C NMR (75 MHz, nyl]-4′-carboxylate (50). Reaction of 23 (152 mg, 0.4 mmol)
CDCl3) δ 165.9, 160.4, 150.9, 150.4, 138.2, 135.0, 134.0, 133.2, and methyl iodide (284 mg, 2.0 mmol) using KOH (112 mg,
132.5, 131.2, 130.9, 128.8, 128.3, 128.1, 127.8, 127.5, 127.5, 2.0 mmol) afforded 50 (149 mg, 85%) as a solid: mp 83–85 °C;
127.4, 126.6, 126.5, 125.4, 123.4, 118.4, 117.9, 114.6, 105.2; IR 1H NMR (300 MHz, CDCl3) δ 7.43–7.30 (7H, m), 7.00 (1H, s),
(KBr) 3424, 3055, 1672, 1612, 1265, 857, 748 cm−1; HRMS m/z 6.78–6.74 (1H, m), 3.87 (3H, s), 3.72 (3H, s), 3.67 (3H, s), 2.23
(M+) calcd for C29H18O3: 414.1256. Found: 414.1254.
(3H, s); 13C NMR (75 MHz, CDCl3) δ 167.7, 156.2, 155.3, 145.3,
9-Cyclopropyl-7-hydroxy-6H-benzo[c]chromen-6-one
(44). 140.6, 134.0, 133.1, 131.4, 131.0, 129.2, 129.0, 128.1, 127.6,
Reaction of 1m (188 mg, 1.0 mmol) and β-ketoester 2a 127.2, 126.6, 112.6, 112.0, 61.8, 55.5, 51.7, 13.6; IR (KBr) 3018,
(195 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) 1712, 1614, 1548, 1405, 1273, 1163, 749 cm−1; HRMS m/z (M+)
afforded 44 (181 mg, 72%) as a solid: mp 140–142 °C; 1H NMR calcd for C23H21BrO4: 440.0623. Found: 440.0622.
(300 MHz, CDCl3) δ 11.19 (1H, s), 7.91 (1H, d, J = 7.5 Hz),
Methyl 5′-(2,4-dimethoxyphenyl)-3,3′-dimethoxy-[1,1′:2′,1″-
7.42–7.37 (1H, m), 7.28–7.19 (3H, m), 6.59 (1H, s), 1.95–1.89 terphenyl]-4′-carboxylate (51). Reaction of 30 (169 mg,
(1H, m), 1.12–1.04 (2H, m), 0.85–0.78 (2H, m); 13C NMR 0.4 mmol) and methyl iodide (284 mg, 2.0 mmol) using KOH
(75 MHz, CDCl3) δ 165.1, 162.4, 155.5, 150.6, 134.7, 130.3, (112 mg, 2.0 mmol) afforded 51 (164 mg, 85%) as a solid: mp
124.8, 123.1, 118.2, 117.6, 112.4, 109.8, 103.6, 16.5, 10.7; IR 68–70 °C; 1H NMR (300 MHz, CDCl3) δ 7.27–7.24 (7H, m), 7.09
(KBr) 3394, 3069, 1663, 1563, 1422, 1333, 1276, 1207, 1080, (1H, t, J = 8.1 Hz), 6.72–7.8 (2H, d, J = 7.8 Hz), 6.57–6.54 (3H,
986, 759 cm−1; HRMS m/z (M+) calcd for C16H12O3: 252.0786. m), 3.86 (3H, s), 3.79 (3H, s), 3.70 (3H, s), 3.57 (3H, s), 3.38
Found: 252.0785.
(3H, s); 13C NMR (75 MHz, CDCl3) δ 168.1, 160.7, 158.8, 157.2,
9-Cyclopropyl-7-hydroxy-8-phenyl-6H-benzo[c]chromen-6-one 155.2, 143.5, 141.8, 137.0, 136.0, 132.9, 131.2, 130.9, 128.7,
(45). Reaction of 1m (188 mg, 1.0 mmol) and β-ketoester 2c 128.6, 127.8, 127.7, 126.7, 122.2, 121.4, 114.9, 113.0, 104.3,
(288 mg, 1.5 mmol) using Cs2CO3 (650 mg, 2.0 mmol) 98.4, 61.5, 55.3, 55.0, 51.8; IR (KBr) 2935, 1731, 1608, 1458,
afforded 45 (200 mg, 61%) as a solid: mp 187–190 °C; 1H NMR 1282, 1159, 1039, 703 cm−1; HRMS m/z (M+) calcd for
(300 MHz, CDCl3) δ 11.60 (1H, s), 7.99 (1H, d, J = 7.2 Hz), C30H28O6: 484.1886. Found: 384.1886.
7.51–7.31 (8H, m), 7.03 (1H, s), 1.83–1.76 (1H, m), 1.00–0.92
Methyl
5′-bromo-5-(2,5-dimethylthiophen-3-yl)-2′,3-
(2H, m), 0.90–0.84 (2H, m); 13C NMR (75 MHz, CDCl3) δ 165.5, dimethoxy-[1,1′-biphenyl]-2-carboxylate (52). Reaction of 39
159.4, 152.8, 150.6, 135.3, 133.8, 130.3, 130.0, 128.3, 127.5, (104 mg, 0.4 mmol) and methyl iodide (284 mg, 2.0 mmol)
124.9, 122.9, 118.3, 117.6, 106.2, 103.5, 14.6, 10.9; IR (KBr) using KOH (112 mg, 2.0 mmol) afforded 52 (141 mg, 80%) as a
3449, 3048, 1661, 1614, 1548, 1405, 1273, 1163, 760 cm−1
;
solid: mp 140–142 °C; 1H NMR (300 MHz, CDCl3) δ 7.40–7.35
HRMS m/z (M+) calcd for C22H16O3: 328.1099. Found: (2H, m), 6.91 (1H, s), 6.89 (1H, s), 6.77 (1H, d, J = 8.7 Hz), 6.70
328.1100.
(1H, s), 3.88 (3H, s), 3.71 (3H, s), 3.62 (3H, s), 2.44 (3H, s), 2.42
(3H, s); 13C NMR (75 MHz, CDCl3) δ 167.5, 156.7, 155.3, 139.4,
137.2, 137.0, 136.0, 133.0, 132.7, 131.5, 131.1, 126.8, 123.2, 121.1,
General procedure for the synthesis of terphenyls (49–54)
To a solution of KOH (2.0 mmol) in DMSO (3.5 mL) and water 112.5, 112.1, 110.7, 56.0, 55.5, 51.7, 15.0, 14.0; IR (KBr) 2939,
(0.5 mL), CH3I (2.0 mmol) and benzo[c]chromen-6-ones 2369, 1733, 1599, 1443, 1251, 1108, 1072, 756, 704 cm−1; HRMS
(0.4 mmol) were added and the reaction mixture was stirred at m/z (M+) calcd for C22H21BrO4S: 460.0344. Found: 460.0342.
928 | Org. Biomol. Chem., 2014, 12, 919–930
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Methyl
2′,3-dimethoxy-4-methyl-5-(naphthalen-2-yl)-[1,1′-
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biphenyl]-2-carboxylate (53). Reaction of 29 (140 mg,
0.4 mmol) and methyl iodide (284 mg, 2.0 mmol) using KOH
(112 mg, 2.0 mmol) afforded 53 (128 mg, 78%) as a solid: mp
113–115 °C; 1H NMR (300 MHz, CDCl3) δ 7.81–7.78 (3H, m),
7.72 (1H, s), 7.42–7.39 (3H, m), 7.25–7.17 (2H, m), 7.07 (1H, s),
6.92–6.82 (2H, m), 3.83 (3H, s), 3.69 (3H, s), 3.57 (3H, s), 2.2
(3H, s); 13C NMR (75 MHz, CDCl3) δ 167.8, 156.0, 155.5, 144.7,
138.2, 135.3, 132.9, 132.2, 130.5, 128.8, 128.7, 128.5, 127.9,
127.8, 127.7, 127.4, 127.3, 127.2, 126.8, 126.0, 125.8, 120.3,
110.3, 61.6, 55.1, 51.5, 13.5; IR (KBr) 3067, 1688, 1618, 1272,
1124, 751 cm−1; HRMS m/z (M+) calcd for C27H24O4: 412.1675.
Found: 412.1676.
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Methyl 5′-cyclopropyl-2,3′-dimethoxy-[1,1′:4′,1″-terphenyl]-2′-
carboxylate (54). Reaction of 45 (131 mg, 0.4 mmol) and
methyl iodide (284 mg, 2.0 mmol) using KOH (112 mg,
2.0 mmol) afforded 54 (133 mg, 86%) as a solid: mp 85–87 °C;
1H NMR (300 MHz, CDCl3) δ 7.39–7.18 (7H, m), 6.94 (1H, d, J =
7.5 Hz), 6.87 (1H, d, J = 8.4 Hz), 6.61 (1H, s), 3.71 (3H, s), 3.54
(3H, s), 3.32 (1H, s), 1.68–1.59 (1H, m), 0.74–0.61 (4H, m); 13C
NMR (75 MHz, CDCl3) δ 167.9, 156.1, 154.9, 144.9, 137.4,
136.3, 135.0, 130.6, 130.5, 129.2, 129.0, 127.9, 127.0, 125.5,
121.5, 120.5, 110.5, 61.6, 55.3, 51.6, 13.5, 9.8; IR (KBr) 3009,
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2942, 2842, 1731, 1604, 1544, 1280, 1143, 1022, 757, 706 cm−1
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HRMS m/z (M+) calcd for C25H24O4: 388.1675. Found:
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388.1673.
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Crystal refinement data for compound 26
C44H36O6, M = 660.73, triclinic, space group Pbca, a = 10.8607
(14) Å, b = 10.8607(14) Å, c = 15.2714(19) Å, V = 1644.3(4) Å3,
Z = 2, T = 200(2) K, ρcalcd = 1.335 mg m−3, 2θmax. = 26.08, refine-
ment of 459 parameters on 6463 independent reflections out
of 10 459 collected reflections (Rint = 0.0454) led to R1 = 0.0642
[I > 2σ(I)], wR2 = 0.2354 (all data) and S = 1.030 with the largest
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difference peak and hole of 0.307 and −0.429
respectively.
e
Å−3
Acknowledgements
This work was supported by the 2013 Yeungnam University
Research Grant (213A367018).
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