Synthesis of 6 H -dibenzo[ b, d ]pyran-6-one derivatives via coumarin-fused cyclohexa-1,3-diene intermediates

Article abstract of DOI:10.1055/s-0031-1289810

In the presence of trifluoroacetic acid and methanesulfonic acid (MSA), a series of monohydric and polyhydric phenols readily undergo a domino Pechmann-dehydration reaction with various 4-hydroxy-6-oxocyclohexane-1,3- dicarboxylates to give 7,8-dihydro-6H-dibenzo[b,d]pyran-6-ones. Subsequent dehydrogenation of the 7,8-dihydro-6H-dibenzo[b,d]pyran-6-ones was performed expediently with DBU/BrCCl₃ to give various 6H-dibenzo[b,d]pyran-6- one derivatives. This strategy has the advantages of inexpensive and easily available raw materials, metal-free procedure, mild reaction conditions, good compatibility with various functional groups, and satisfactory yields. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289810

PAPER
▌2385
paper
Synthesis of 6H-Dibenzo[b,d]pyran-6-one Derivatives via Coumarin-Fused
Cyclohexa-1,3-diene Intermediates
Synthesis of 6H-Dibenzo[b,d]pyran-6-ones
Chao-Yue Chen,a Yong-Sheng Zhao,a Chang-Bing Xiang,a Zhi-Zhen Huang*a,b
a
School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. of China
b
Department of Chemistry, Zhejiang University, Hangzhou 310028, P. R. of China
Fax +86(25)83686240; E-mail: huangzz@nju.edu.cn
Received: 10.04.2012; Accepted after revision: 14.05.2012
modulating effects.1–4 In addition, 6H-dibenzo[b,d]pyran-
Abstract: In the presence of trifluoroacetic acid and methanesul-
6-ones are key intermediates in the synthesis of cannibi-
fonic acid (MSA), a series of monohydric and polyhydric phenols
nol/cannabinoids and other related natural products.3d,5
readily undergo a domino Pechmann–dehydration reaction with
various 4-hydroxy-6-oxocyclohexane-1,3-dicarboxylates to give
There are many strategies for the synthesis of the couma-
7,8-dihydro-6H-dibenzo[b,d]pyran-6-ones. Subsequent dehydroge- rin derivatives, 6H-dibenzo[b,d]pyran-6-ones 1.3d,6,7
nation of the 7,8-dihydro-6H-dibenzo[b,d]pyran-6-ones was per-
formed expediently with DBU/BrCCl3 to give various 6H-
Among them, the Pechmann reaction of 2-oxocyclohex-
anecarboxylates 2 with phenols to form coumarin-fused
dibenzo[b,d]pyran-6-one derivatives. This strategy has the advan-
cyclohexenes, 7,8,9,10-tetrahydro-6H-dibenzo[b,d]py-
tages of inexpensive and easily available raw materials, metal-free
ran-6-ones 3, followed by dehydrogenation to give 6H-
procedure, mild reaction conditions, good compatibility with vari-
dibenzo[b,d]pyran-6-ones 1 is a straightforward and expe-
dient strategy (Scheme 1).7 However, this strategy suffers
from poor yields or undesired side reactions in the dehy-
drogenation step in many cases. For example, Sawada et
al. constructed a lactone ring by Pechmann condensation
of a 2-oxocyclohexanecarboxylate with a phenol, but sub-
sequent dehydrogenation with 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone led to 6H-dibenzo[b,d]pyran-6-one de-
rivatives in only 22.5–23.8% yields, except in one exam-
ple (61% yield).7a Carotti and co-workers also prepared
7,8,9,10-tetrahydro derivatives 3 by Pechmann reaction,
however, phenolic hydroxyl groups were protected by
methylation before oxidative dehydrogenation and later
deprotected to avoid side reactions.7b Chebaane et al.7c
also encountered side reactions, such as hydrogenolysis of
an ester group and loss of a functional group, in the dehy-
ous functional groups, and satisfactory yields.
Key words: 6H-dibenzo[b,d]pyran-6-one, 7,8-dihydro-6H-diben-
zo[b,d]pyran-6-one, domino Pechmann–dehydration reaction, oxi-
dative dehydrogenation, synthesis
6H-Dibenzo[b,d]pyran-6-ones (6H-benzo[c]chromen-6-
ones) 1 (Scheme 1) are an important group of coumarin
derivatives that have a fused tricyclic nucleus; they are
found as components of the structures in urolithins,1 gra-
phislactones,2 gilvocarcins,3 defuco-gilvocarcins,3b,4 and
chrysomycins.2c,3d,e,4 They are usually isolated from plant
and animal sources and are metabolic products of micro-
organisms.1–4 Many of them possess a wide spectrum of
biological activity, spanning from antibacterial, antitu-
mor, antiallergic, antioxidant, and antibiotic to immuno-
previous work
O
EtO
O
O
R1
O
R2
R2
2
5
O
4
1
3
O
6
3
2
coumarin-fused cyclo-
hexene intermediate
OH
R1
R1
7
R2
this work
8
10
O
O
9
O
EtO
R1
1
O
R2
R2
4
coumarin-fused cyclo-
hexa-1,3-diene intermediate
OH
5
Scheme 1 Strategies for the synthesis of 6H-dibenzo[b,d]pyran-6-ones
SYNTHESIS 2012, 44, 2385–2395
Advanced online publication: 04.07.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0031-1289810; Art ID: SS-2012-H0348-OP
© Georg Thieme Verlag Stuttgart · New York

2386
C.-Y. Chen et al.
PAPER
drogenation of 7,8,9,10-tetrahydro derivatives 3 with pal- of its dehydrated product, 7,8-dihydro-6H-diben-
ladium on carbon.
zo[b,d]pyran-6-one 4k. Considering that 4k is the product
of the further dehydration reaction of 3a, we next attempt-
ed to enhance the yield of the domino Pechmann–dehy-
dration reaction by optimizing the reaction conditions. We
found that using methanesulfonic acid (MSA), polyphos-
phoric acid, and trifluoroacetic acid, which are common
Pechmann condensation catalysts, increased the yield of
4k (entries 2–4); the best yield of 4k (58%) was obtained
with trifluoroacetic acid (entry 4). The addition of a dehy-
drant, such as anhydrous copper sulfate, 4Å molecular
sieve, phosphorus pentoxide, 4-toluenesulfonic acid,
methanesulfonic acid, or various additives, such as palla-
dium(II) acetate,10 molecular iodine,11 and potassium io-
dide, was found to increase the yield of 4k further (entries
5–12); the best yield was obtained by using methanesul-
fonic acid as a dehydrant (entry 12). Screening of a range
of reaction temperatures indicated that reflux in trifluoro-
acetic acid led to best yield of 4k. Therefore, the domino
Pechmann–dehydration reaction was performed in the
presence of trifluoroacetic acid and methanesulfonic acid
at reflux.
Considering the drawbacks in the dehydrogenation of the
cyclohexene moiety in 3, we envisioned employing 4-hy-
droxy-6-oxocyclohexane-1,3-dicarboxylate derivatives 5
to
form
9-hydroxy-7,8,9,10-tetrahydro-6H-diben-
zo[b,d]pyran-6-ones by Pechmann reaction. Subsequent
dehydration would lead to coumarin-fused cyclohexa-1,3-
dienes, 7,8-dihydro-6H-dibenzo[b,d]pyran-6-ones 4. The
conjugated system in the cyclohexa-1,3-diene moiety of 4
may be beneficial to the dehydrogenation, thus forming
the desired benzene ring in 1 with increased yield. Met-
wally and co-workers prepared two examples of 7,8-di-
hydro-6H-dibenzo[b,d]pyran-6-ones 4 in 40% or 55%
yields by the reaction of 4-hydroxy-6-oxocyclohexane-
1,3-dicarboxylate derivatives with phenols in the presence
of polyphosphoric acid;8 they were not taken further and
used for the synthesis of 6H-dibenzo[b,d]pyran-6-one de-
rivatives 1. Therefore, our aims were to increase the yields
of 7,8-dihydro-6H-dibenzo[b,d]pyran-6-ones 4 and to ex-
plore the subsequent dehydrogenation reaction in the syn-
thesis of 6H-dibenzo[b,d]pyran-6-ones 1.
Under the optimized reaction conditions, it was found that
a series of monohydric and polyhydric phenols underwent
the domino Pechmann–dehydration reaction readily with
various 4-hydroxy-6-oxocyclohexane-1,3-dicarboxylate
derivatives 5a–e to give the desired 7,8-dihydro-6H-
dibenzo[b,d]pyran-6-ones 4a–q in 54–86% yields (Table
2). Both aromatic and aliphatic 4-hydroxy-6-oxocyclo-
Initially, ethyl 4-hydroxy-4-methyl-6-oxo-2-phenylcy-
clohexane-1,3-dicarboxylate (5a), which was easily pre-
pared by the reaction of benzaldehyde with ethyl
acetoacetate,9 was employed in the reaction with resorcin-
ol in the presence of 12.0 M sulfuric acid (Table 1, entry
1); the Pechmann product, 3-hydroxycyclohex-2-ene de-
rivative 3a, was isolated in 21% yield with a small amount
Table 1 Optimization of the Domino Pechmann–Dehydration Reaction
HO
O
O
HO
O
O
O
O
O
reaction
conditions
HO
OH
+
+
EtO
OEt
OEt
OEt
HO
OH
5a
O
O
3a
4k
Entry
Acid
Additive
Temp (°C)
Time (h)
Yield (%) of 4k
1
H2SO4
MSA
PPA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
TFA
–
–
–
–
0–r.t.
80
24
24
24
24
24
24
24
24
24
24
24
24
11
37
52
58
61
63
55
59
67
61
82
84
2
3
100
4
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
5
Pd(OAc)2
I2
6
7
KI
8
4 Å MS
CuSO4
P2O5
9
10
11
12
TsOH
MSA
Synthesis 2012, 44, 2385–2395
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 6H-Dibenzo[b,d]pyran-6-ones
2387
hexane-1,3-dicarboxylate derivatives 5a–e performed the ino reaction tolerated a variety of functional groups such
reaction smoothly. Like other Pechmann condensa- as ether, ester, hydroxyl, and nitro groups. The structure
tions,11,12 monohydric phenols bearing electron-donating of 7,8-dihydro-6H-dibenzo[b,d]pyran-6-one 4k was fur-
groups in the meta position of phenolic hydroxyl group ther confirmed by single crystal X-ray diffraction (Figure
1
gave better yields, probably because an electron-donating 1). The X-ray analysis also showed why in the H NMR
group increased the electron density at the para position spectrum of 4k, no coupling effect between the adjacent
for electrophilic attack. 3-Methylphenol led to lower protons H4 and H9 is found because the dihedral angle be-
yields and needed longer times. Phenol itself and some tween C4–C9–H and C9–C4–H bonds in the rigid cycle is
phenols bearing electron-withdrawing groups, such as 3- 87.166°.13
nitrophenol and 3-chlorophenol failed to react. The dom-
Table 2 Formation of 7,8-Dihydro-6H-dibenzo[b,d]pyran-6-ones 4a–q by Domino Pechmann–Dehydration Reactions
O
O
O
R2
O
OH
R1
TFA-MSA
reflux
R2
O
EtO
OEt
R1
+
OEt
O
monohydric, dihydric
or trihydric phenols
OH
5a–e
5b: R2 = 4-O2NC6H4
5a: R2 = Ph
4a–q
5c: R2 = 4-MeC6H4 5d: R2 = H
5e: R2 = Me
Entry
1
Phenol
Oxodioate 5
Time (h)
40
Product 4a–q
Yield (%)
O
O
OH
OH
5a
4a
55
O
O
O
O
NO2
2
3
4
5
6
5b
5e
5a
5d
5a
40
30
30
40
40
4b
4c
4d
4e
4f
57
66
68
60
62
O
O
MeO
MeO
AcO
AcO
O
O
O
O
O
O
O
O
MeO
MeO
AcO
AcO
OH
OH
OH
OH
O
O
O
O
O
O
O
O
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2385–2395

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C.-Y. Chen et al.
PAPER
Table 2 Formation of 7,8-Dihydro-6H-dibenzo[b,d]pyran-6-ones 4a–q by Domino Pechmann–Dehydration Reactions (continued)
R2
O
O
O
O
O
OH
R1
TFA-MSA
reflux
R2
O
EtO
OEt
R1
+
OEt
monohydric, dihydric
or trihydric phenols
OH
5a–e
5b: R2 = 4-O2NC6H4
5a: R2 = Ph
4a–q
5c: R2 = 4-MeC6H4 5d: R2 = H
5e: R2 = Me
Entry
7
Phenol
Oxodioate 5
Time (h)
40
Product 4a–q
Yield (%)
AcO
O
O
NO2
AcO
OH
5b
4g
64
O
O
O
O
O
OH
8
5a
5d
5e
5a
5c
5b
40
24
24
24
24
24
4h
4i
54
72
76
84
80
86
O
HO
HO
HO
HO
HO
O
O
HO
HO
HO
HO
HO
OH
9
O
O
O
O
O
O
O
O
O
O
OH
OH
OH
OH
10
11
12
13
4j
O
O
O
O
O
O
O
O
4k
4l
CH3
NO2
4m
OH
HO
O
O
OH
HO
OH
14
5a
24
4n
77
O
O
Synthesis 2012, 44, 2385–2395
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 6H-Dibenzo[b,d]pyran-6-ones
2389
Table 2 Formation of 7,8-Dihydro-6H-dibenzo[b,d]pyran-6-ones 4a–q by Domino Pechmann–Dehydration Reactions (continued)
O
O
O
R2
O
OH
R1
TFA-MSA
reflux
R2
O
EtO
OEt
R1
+
OEt
O
monohydric, dihydric
or trihydric phenols
OH
5a–e
5b: R2 = 4-O2NC6H4
5a: R2 = Ph
4a–q
5c: R2 = 4-MeC6H4 5d: R2 = H
5e: R2 = Me
Entry
15
Phenol
Oxodioate 5
Time (h)
Product 4a–q
Yield (%)
OH
HO
HO
HO
O
O
O
O
O
O
NO2
OH
HO
OH
OH
5b
24
4o
79
O
O
O
O
O
O
HO
HO
16
17
5a
5b
24
24
4p
4q
63
66
OH
OH
OH
OH
NO2
OH
Next, for the dehydrogenation or aromatization of the cy- Various 7,8-dihydro-6H-dibenzo[b,d]pyran-6-ones 4a–q
clohexadiene moiety in 4, 4k was chosen as a model reac- were examined in the dehydrogenative reaction. We
tant to explore and optimize the reaction conditions. Our found that 4a–q could react with 1,8-diazabicyc-
experiments showed that many dehydrogenative reagents, lo[5.4.0]undec-7-ene
and
bromotrichloromethane
such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, sele- smoothly at 0 °C to room temperature to give the desired
nium dioxide, activated manganese dioxide, molecular io- 6H-dibenzo[b,d]pyran-6-ones 1a–q in satisfactory yields
dine, cerium(IV) ammonium nitrate, (CAN), and 10% (Table 3). The experimental results also indicated that a
palladium on carbon were not effective for the dehydroge- variety of functional groups, such as ether, ester, hydroxyl
nation. Gratifyingly, when 1,8-diazabicyclo[5.4.0]undec- and nitro groups, are compatible with the reaction. The
7-ene was employed with bromotrichloromethane, the de- structure of 6H-dibenzo[b,d]pyran-6-one derivative 1l
hydrogenation of 4k occurred readily in acetonitrile.14
was determined further by single crystal X-ray diffraction
(Figure 2).
Figure 1 X-ray crystal structure of 4k
Figure 2 X-ray crystal structure of 1l
© Georg Thieme Verlag Stuttgart · New York
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2390
C.-Y. Chen et al.
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Table 3 Oxidative Dehydrogenation for 6H-Dibenzo[b,d]pyran-6-ones 1
R1
R1
R2
O
O
R2
O
O
BrCCl3-DBU
0 °C–r.t.
R4
O
R4
O
R3
O
R3
O
4
1
Entry
R1
R2
R3
R4
Ph
Product
Yield (%)
1
H
Me
Me
H
1a
1b
1c
1d
1e
1f
73
75
79
72
64
61
67
64
72
76
72
69
75
51
54
52
48
2
H
H
4-O2NC6H4
3
H
OMe
OMe
OAc
OAc
OAc
Me
H
Me
4
H
H
Ph
5
H
H
H
6
H
H
Ph
7
H
H
4-O2NC6H4
1g
1h
1i
8
H
Me
H
Ph
9
H
OH
H
10
11
12
13
14
15
16
17
H
OH
H
Me
1j
H
OH
H
Ph
1k
1l
H
OH
H
4-MeC6H4
4-O2NC6H4
Ph
H
OH
H
1m
1n
1o
1p
1q
OH
OH
H
OH
H
OH
H
4-O2NC6H4
Ph
OH
OH
OH
H
OH
4-O2NC6H4
In conclusion, we have found that monohydric and poly- and practical method for the synthesis of 6H-diben-
hydric phenols readily undergo domino Pechmann– zo[b,d]pyran-6-one derivatives.
dehydration reaction with various 4-hydroxy-6-oxocyclo-
hexane-1,3-dicarboxylate derivatives 5a–e in the pres-
1
The H NMR and 13C NMR spectra were recorded on a Bruker
ence of trifluoroacetic acid and methanesulfonic acid to
give 7,8-dihydro-6H-dibenzo[b,d]pyran-6-ones 4a–q in
54–86% yields. Subsequent dehydrogenation of 7,8-di-
hydro-6H-dibenzo[b,d]pyran-6-ones 4 with 1,8-diazabi-
cyclo[5.4.0]undec-7-ene and bromotrichloromethane,
gave 6H-dibenzo[b,d]pyran-6-ones 1 in 48–79% yields.
This strategy has the advantages of satisfactory yields and
mild reaction conditions. Furthermore: (1) It employs in-
expensive and easily available raw materials, such as eth-
yl acetoacetate, aromatic/aliphatic aldehydes and phenols.
(2) It tolerates various functional groups, such as ether, es-
ter, hydroxyl, and nitro groups, thereby obviating protec-
tion and deprotection steps. (3) It is carried out under
metal-free conditions; this is more environmentally
friendly. Therefore, this novel strategy affords an efficient
ARX-300 (300 MHz) NMR spectrometer with TMS as internal
standard. MS (ESI) spectra were obtained on a Finnigan-Mat LCQ
mass spectrometer (Thermo Fisher Scientific, USA). Melting points
were determined on an electrically heated RK-Z melting point ap-
paratus (Analytical Instrument Factory in Tianjin, China) and are
uncorrected. Elemental analyses were carried out on an Elementar
Vario MICRO CUBE (Germany). Purification by flash column
chromatography was performed using silica gel (200–300 mesh) as
the stationary phase and mixtures of hexanes and EtOAc as the mo-
bile phase. Solvents were purified according to standard proce-
dures.
4-Hydroxy-6-oxocyclohexane-1,3-dicarboxylate 5a–e
Compounds 5a–e were prepared according to literature methods.9
Diethyl 4-Hydroxy-4-methyl-6-oxo-2-phenylcyclohexane-1,3-
dicarboxylate (5a)9a
White solid; mp 153–155 °C (Lit.9a 156 °C).
Synthesis 2012, 44, 2385–2395
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 6H-Dibenzo[b,d]pyran-6-ones
2391
Diethyl 4-Hydroxy-4-methyl-2-(4-nitrophenyl)-6-oxocyclohex-
ane-1,3-dicarboxylate (5b)9a
MS (ESI): m/z [M + H]+ calcd for C19H21O5: 329.14; found: 328.90.
Anal. Calcd for C19H20O5: C, 69.50; H, 6.14. Found: C, 69.62; H,
6.11.
White solid; mp 187–189 °C (Lit.9a 188 °C).
Diethyl 4-Hydroxy-4-methyl-2-(4-methylphenyl)-6-oxocyclo-
hexane-1,3-dicarboxylate (5c)9b
Ethyl 3-Methoxy-9-methyl-6-oxo-7-phenyl-7,8-dihydro-6H-
dibenzo[b,d]pyran-8-carboxylate (4d)
Yellow solid; yield: 1.06 g (68%); mp 145–147 °C.
Colorless needles; mp144–146 °C (Lit.9b 146 °C).
1H NMR (300 MHz, DMSO-d6): δ = 7.97 (d, J = 8.7 Hz, 1 H), 7.28–
7.17 (m, 5 H), 7.10 (d, J = 0.9 Hz, 1 H), 7.01–6.96 (m, 2 H), 4.66 (s,
1 H), 4.14–4.03 (m, 2 H), 3.85 (s, 3 H), 3.51 (s, 1 H), 2.04 (s, 3 H),
1.14 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 170.8, 162.6, 160.8, 155.1,
144.2, 142.2, 141.1, 129.1, 127.5, 126.1, 118.3, 114.3, 112.8, 110.7,
101.5, 61.4, 56.4, 51.9, 39.2, 24.6, 14.4.
Diethyl 4-Hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxyl-
ate (5d)9c
Colorless liquid.
Diethyl 4-Hydroxy-2,4-dimethyl-6-oxocyclohexane-1,3-dicar-
boxylate (5e)9d
White solid; mp 74–77 °C (Lit.9d 75–77 °C).
7,8-Dihydro-6H-dibenzo[b,d]pyran-6-ones 4a–q; General Pro-
cedure
MS (ESI): m/z [M + H]+ calcd for C24H23O5: 391.15; found: 391.15.
A mixture of the phenol derivative (4.2 mmol) and 5a–e (4.0 mmol)
in TFA (20 mL) and MSA (1.0 mL) was refluxed for the time indi-
cated in Table 2. After completion of the reaction, TFA in the mix-
ture was evaporated in vacuo. To the resulting mixture, was added
EtOAc (50 mL). The mixture was washed with sat. aq NaHCO3 (50
mL) to neutralize acid. The aqueous layer was extracted with
EtOAc (2 × 50 mL). The combined organic layers were washed
with brine, dried (anhyd Na2SO4), and concentrated. The residue
was purified by column chromatography (silica gel, EtOAc–
hexane, 1:2 to 1:1) to afford 4a–q.
Anal. Calcd for C24H22O5: C, 73.83; H, 5.68. Found: C, 73.73; H,
5.73.
Ethyl 3-Acetoxy-9-methyl-6-oxo-7,8-dihydro-6H-diben-
zo[b,d]pyran-8-carboxylate (4e)
White solid; yield: 0.822 g (60%); mp 163–166 °C.
1H NMR (300 MHz, DMSO-d6): δ = 7.74 (d, J = 9.0 Hz, 1 H), 6.85
(s, 1 H), 6.72 (dd, J = 9.0, 2.4 Hz, 1 H), 6.66 (d, J = 2.1 Hz, 1 H),
4.01 (q, J = 9.0 Hz, 2 H), 3.44 (dd, J = 8.4, 4.2 Hz, 1 H), 3.12 (dd,
J = 17.4, 4.2 Hz, 1 H), 2.64 (dd, J = 17.4, 8.4 Hz, 1 H), 2.17 (s, 3 H),
2.08 (s, 3 H), 1.14 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 171.2, 163.2, 160.7, 160.0,
154.1, 144.9, 140.2, 125.1, 117.7, 112.6, 111.3, 110.4, 103.2, 61.4,
42.2, 24.4, 23.1, 20.5, 14.3.
Ethyl 3,9-Dimethyl-6-oxo-7-phenyl-7,8-dihydro-6H-diben-
zo[b,d]pyran-8-carboxylate (4a)
Yellow solid; yield: 0.824 g (55%); mp 185–187 °C (Lit.8 185 °C).
1H NMR (300 MHz, CDCl3): δ = 7.67 (d, J = 8.7 Hz, 1 H), 7.29–
7.20 (m, 5 H), 7.15–7.12 (m, 2 H), 6.85 (d, J = 1.2 Hz, 1 H), 4.81 (s,
1 H), 4.16 (q, J = 7.2 Hz, 2 H), 3.41 (s, 1 H), 2.45 (s, 3 H), 2.09 (d,
J = 1.2 Hz, 3 H), 1.25 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 170.7, 161.2, 153.6, 143.4, 142.2,
141.3, 140.9, 128.7, 127.28, 127.25, 125.3, 123.4, 117.8, 117.4,
116.9, 114.9, 61.5, 52.4, 39.7, 24.7, 21.6, 14.1.
MS (ESI): m/z [M + H]+ calcd for C19H19O6: 343.12; found: 343.16.
Anal. Calcd for C19H18O6: C, 66.66; H, 5.30. Found: C, 66.57; H,
5.27.
Ethyl 3-Acetoxy-9-methyl-6-oxo-7-phenyl-7,8-dihydro-6H-
dibenzo[b,d]pyran-8-carboxylate (4f)
White solid; yield: 1.04 g (62%); mp 173–176 °C.
MS (ESI): m/z [M + H]+ calcd for C24H23O4: 375.16; found: 375.15.
1H NMR (300 MHz, CDCl3): δ = 7.80 (d, J = 8.1 Hz, 1 H), 7.27–
7.22 (m, 5 H), 7.12–7.08 (m, 2 H), 6.82 (d, J = 1.5 Hz, 1 H), 4.81 (s,
1 H), 4.17 (q, J = 7.2 Hz, 2 H), 3.41 (s, 1 H), 2.34 (s, 3 H), 2.10 (d,
J = 1.2 Hz, 3 H), 1.26 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 170.6, 168.9, 160.6, 154.0, 152.6,
144.0, 140.9, 140.5, 128.8, 127.4, 127.2, 124.5, 118.0, 117.6, 117.5,
115.3, 110.6, 61.6, 52.4, 39.7, 24.7, 21.1, 14.1.
Anal. Calcd for C24H22O4: C, 76.99; H, 5.92. Found: C, 76.87; H,
5.88.
Ethyl 3,9-Dimethyl-7-(4-nitrophenyl)-6-oxo-7,8-dihydro-6H-
dibenzo[b,d]pyran-8-carboxylate (4b)
Yellow solid; yield: 0.956 g (57%); mp 150–152 °C.
1H NMR (300 MHz, CDCl3): δ = 8.08 (d, J = 8.4 Hz, 2 H), 7.68 (d,
J = 8.4 Hz, 1 H), 7.44 (d, J = 8.4 Hz, 2 H), 7.16–7.13 (m, 2 H), 6.89
(s, 1 H), 4.91 (s, 1 H), 4.16 (q, J = 7.2 Hz, 2 H), 3.36 (s, 1 H), 2.44
(s, 3 H), 2.12 (s, 3 H), 1.24 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 170.0, 160.9, 153.6, 148.4, 147.2,
143.4, 142.9, 142.0, 128.3, 125.5, 124.0, 123.5, 118.0, 117.5, 115.6,
114.6, 61.9, 51.9, 39.5, 24.7, 21.6, 14.1.
MS (ESI): m/z [M + H]+ calcd for C25H23O6: 419.15; found: 419.20.
Anal. Calcd for C25H22O6: C, 71.76; H, 5.30. Found: C, 71.84; H,
5.27.
Ethyl 3-Acetoxy-9-methyl-7-(4-nitrophenyl)-6-oxo-7,8-di-
hydro-6H-dibenzo[b,d]pyran-8-carboxylate (4g)
White solid; yield: 1.09 g (64%); mp 141–144 °C.
1H NMR (300 MHz, CDCl3): δ = 8.06 (d, J = 9.0 Hz, 2 H), 7.80 (d,
J = 9.6 Hz, 1 H), 7.41 (d, J = 9.0 Hz, 2 H), 7.11–7.07 (m, 2 H), 6.85
(d, J = 1.2 Hz, 1 H), 4.89 (s, 1 H), 4.14 (q, J = 6.9 Hz, 2 H), 3.36 (s,
1 H), 2.30 (s, 3 H), 2.10 (s, 3 H), 1.22 (t, J = 6.9 Hz, 3 H).
MS (ESI): m/z [M + H]+ calcd for C24H22NO6: 420.14; found:
419.95.
Anal. Calcd for C24H21NO6: C, 68.73; H, 5.05; N, 3.34. Found: C,
68.79; H, 5.01; N, 3.37.
Ethyl 3-Methoxy-7,9-dimethyl-6-oxo-7,8-dihydro-6H-diben-
zo[b,d]pyran-8-carboxylate (4c)
Yellow solid; yield: 0.867 g (66%); mp 84–86 °C.
13C NMR (75 MHz, CDCl3): δ = 169.9, 168.8, 160.5, 154.1, 153.0,
148.2, 147.9, 147.2, 144.1, 141.7, 137.5, 128.3, 124.7, 124.0, 118.3,
117.7, 110.7, 61.9, 51.8, 39.4, 24.7, 21.1, 14.1.
1H NMR (300 MHz, DMSO-d6): δ = 7.85 (d, J = 9.0 Hz, 1 H), 6.94–
6.89 (m, 3 H), 4.04–3.93 (m, 2 H), 3.82 (s, 3 H), 3.40 (q, J = 7.2 Hz,
1 H), 3.20 (s, 1 H), 2.13 (s, 3 H), 1.08 (t, J = 6.9 Hz, 3 H), 1.03 (d,
J = 7.2 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 171.1, 162.2, 160.8, 154.8,
144.0, 140.2, 125.7, 117.1, 112.6, 110.9, 101.4, 61.0, 56.3, 50.4,
29.4, 24.7, 17.5, 14.4.
MS (ESI): m/z [M + H]+ calcd for C25H22NO8: 464.13; found:
464.10.
Anal. Calcd for C25H21NO8: C, 64.79; H, 4.57; N, 3.02. Found: C,
64.74; H, 4.59; N, 3.01.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2385–2395

2392
C.-Y. Chen et al.
PAPER
Ethyl 1,3,9-Trimethyl-6-oxo-7-phenyl-7,8-dihydro-6H-diben-
zo[b,d]pyran-8-carboxylate (4h)
1 H), 2.76 (d, J = 10.5 Hz, 1 H), 1.33 (s, 3 H), 1.05 (t, J = 7.2 Hz, 3
H).
13C NMR (75 MHz, DMSO-d6): δ = 172.0, 160.7, 159.6, 154.3,
147.2, 144.3, 128.4, 128.3, 126.5, 126.3, 120.1, 113.3, 112.4, 102.4,
68.2, 60.2, 60.2, 58.8, 43.0, 40.4, 28.4, 14.6.
Yellow solid; yield: 0.839 g (54%); mp 155–157 °C.
1H NMR (300 MHz, CDCl3): δ = 7.65 (s, 1 H), 7.17 (s, 1 H), 7.15–
7.14 (m, 3 H), 7.06–7.03 (m, 2 H), 6.84 (s, 1 H), 4.77 (s, 1 H), 4.15
(q, J = 7.2 Hz, 2 H), 3.39 (s, 1 H), 2.45 (s, 3 H), 2.28 (s, 3 H), 2.09
(s, 3 H), 1.24 (t, J = 7.2 Hz, 3 H).
MS (ESI): m/z [M + H]+ calcd for C23H23O6: 395.15; found: 395.10.
Anal. Calcd for C23H22O6: C, 70.04; H, 5.62. Found: C, 70.12; H,
5.67.
13C NMR (75 MHz, CDCl3): δ = 170.8, 161.1, 153.6, 143.3, 142.1,
141.1, 137.9, 136.9, 129.4, 128.9, 127.1, 125.2, 123.3, 117.8, 117.4,
115.0, 61.5, 52.5, 39.4, 24.7, 21.6, 21.0, 14.1.
Ethyl 3-Hydroxy-9-methyl-7-(4-methylphenyl)-6-oxo-7,8-di-
hydro-6H-dibenzo[b,d]pyran-8-carboxylate (4l)
Yellow solid; yield: 1.25 g (80%); mp 124–126 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.54 (s, 1 H), 7.88 (d, J = 8.7
Hz, 1 H), 7.09–7.01 (m, 5 H), 6.84 (dd, J = 8.7, 2.1 Hz, 1 H), 6.75
(d, J = 2.1 Hz, 1 H), 4.57 (s, 1 H), 4.09–4.01 (m, 2 H), 3.44 (s, 1 H),
2.22 (s, 3 H), 2.02 (s, 3 H), 1.14 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 170.8, 161.3, 160.9, 155.1,
144.0, 142.2, 138.2, 136.5, 129.6, 127.3, 126.2, 118.3, 113.5, 109.6,
106.7, 102.9, 61.3, 52.0, 38.8, 24.7, 21.0, 14.4.
MS (ESI): m/z [M + H]+ calcd for C25H25O4: 389.18; found: 389.20.
Anal. Calcd for C25H24O4: C, 77.30; H, 6.23. Found: C, 77.24; H,
6.23.
Ethyl 3-Hydroxy-9-methyl-6-oxo-7,8-dihydro-6H-diben-
zo[b,d]pyran-8-carboxylate (4i)
Yellow solid; yield: 0.865 g (72%); mp 136–138 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.44 (s, 1 H), 7.77 (d, J = 9.0
Hz, 1 H), 6.91 (s, 1 H), 6.77 (dd, J = 9.0, 2.4 Hz, 1 H), 6.70 (d, J =
2.1 Hz, 1 H), 4.03 (dq, J = 9.0, 1.8 Hz, 2 H), 3.42 (dd, J = 8.4, 4.2
Hz, 1 H), 3.09 (dd, J = 17.4, 4.2 Hz, 1 H), 2.68 (dd, J = 17.4, 8.7 Hz,
1 H), 2.10 (s, 3 H), 1.12 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 171.9, 161.1, 160.9, 154.8,
145.7, 141.7, 125.6, 118.2, 113.3, 110.9, 109.8, 102.9, 61.1, 43.3,
24.0, 23.7, 14.4.
MS (ESI): m/z [M + H]+ calcd for C24H23O5: 391.15; found: 391.10.
Anal. Calcd for C24H22O5: C, 73.83; H, 5.68. Found: C, 73.83; H,
5.64.
Ethyl 3-Hydroxy-9-methyl-7-(4-nitrophenyl)-6-oxo-7,8-di-
hydro-6H-dibenzo[b,d]pyran-8-carboxylate (4m)
Yellow solid; yield: 1.45 g (86%); mp 184–187 °C.
MS (ESI): m/z [M + H]+ calcd for C17H17O5: 301.11; found: 301.10.
1H NMR (300 MHz, DMSO-d6): δ = 10.61 (s, 1 H), 8.12 (d, J = 8.7
Hz, 2 H), 7.91 (d, J = 8.7 Hz, 1 H), 7.49 (d, J = 8.7 Hz, 2 H), 7.09
(s, 1 H), 6.85 (dd, J = 9.0, 2.4 Hz, 1 H), 6.76 (d, J = 2.7 Hz, 1 H),
4.76 (s, 1 H), 4.14–4.02 (m, 2 H), 3.58 (s, 1 H), 2.05 (s, 3 H), 1.15
(t, J = 7.5 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 170.4, 161.6, 160.9, 155.3,
149.0, 147.1, 144.1, 142.9, 129.1, 126.4, 124.2, 118.5, 113.7, 112.3,
109.5, 103.0, 61.6, 51.2, 39.0, 24.6, 14.4.
Anal. Calcd for C17H16O5: C, 67.99; H, 5.37. Found: C, 68.04; H,
5.31.
Ethyl 3-Hydroxy-7,9-dimethyl-6-oxo-7,8-dihydro-6H-diben-
zo[b,d]pyran-8-carboxylate (4j)
Yellow solid; yield: 0.955 g (76%); mp 171–174 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.45 (s, 1 H), 7.80 (d, J = 9.0
Hz, 1 H), 6.94 (s, 1 H), 6.79 (dd, J = 8.7, 2.1 Hz, 1 H), 6.71 (d, J =
2.1 Hz, 1 H), 4.06–3.95 (m, 2 H), 3.42–3.37 (m, 1 H), 3.21 (s, 1 H),
2.13 (s, 3 H), 1.10 (t, J = 6.9 Hz, 3 H), 1.03 (d, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 171.2, 160.94, 160.90, 154.8,
143.8, 140.4, 125.8, 117.1, 116.1, 113.4, 109.8, 102.9, 61.0, 50.4,
29.4, 24.8, 17.6, 14.4.
MS (ESI): m/z [M + H]+ calcd for C23H20NO7: 422.12; found:
422.10.
Anal. Calcd for C23H19NO7: C, 65.55; H, 4.54; N, 3.32. Found: C,
65.45; H, 4.49; N, 3.36.
MS (ESI): m/z [M – H]– calcd for C18H17O5: 313.11; found: 313.10.
Ethyl 3,4-Dihydroxy-9-methyl-6-oxo-7-phenyl-7,8-dihydro-6H-
dibenzo[b,d]pyran-8-carboxylate (4n)
Anal. Calcd for C18H18O5: C, 68.78; H, 5.77. Found: C, 68.83; H,
5.67.
Yellow solid; yield: 1.21 g (77%); mp 167–169 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.05 (s, 1 H), 9.39 (s, 1 H),
7.38 (d, J = 9.0 Hz, 1 H), 7.29–7.18 (m, 5 H), 7.02 (d, J = 0.9 Hz, 1
H), 6.85 (d, J = 8.7 Hz, 1 H), 4.62 (s, 1 H), 4.13–4.01 (m, 2 H), 3.48
(s, 1 H), 2.01 (s, 3 H), 1.14 (t, J = 7.5 Hz, 3 H).
Ethyl 3-Hydroxy-9-methyl-6-oxo-7-phenyl-7,8-dihydro-6H-
dibenzo[b,d]pyran-8-carboxylate (4k)
Yellow solid; yield: 1.27 g (84%); mp 190–193 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.56 (s, 1 H), 7.89 (d, J = 9.0
Hz, 1 H), 7.28–7.17 (m, 5 H), 7.06 (d, J = 1.2 Hz, 1 H), 6.85 (dd, J =
8.4, 2.1 Hz, 1 H), 6.76 (d, J = 2.1 Hz, 1 H), 4.63 (s, 1 H), 4.13–4.00
(m, 2 H), 3.48 (s, 1 H), 2.02 (s, 3 H), 1.14 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 170.8, 161.4, 161.0, 155.2,
144.0, 142.3, 141.3, 129.0, 127.5, 127.4, 126.2, 118.4, 113.6, 113.3,
109.6, 103.0, 61.4, 51.9, 39.2, 24.6, 14.4.
13C NMR (75 MHz, DMSO-d6): δ = 170.9, 160.9, 149.6, 143.7,
143.6, 142.7, 141.3, 132.9, 129.0, 127.5, 127.4, 118.6, 115.2, 113.1,
112.9, 110.4, 61.4, 51.9, 39.2, 24.6, 14.4.
MS (ESI): m/z [M + H]+ calcd for C23H21O6: 393.13; found: 393.10.
Anal. Calcd for C23H20O6: C, 70.40; H, 5.14. Found: C, 70.32; H,
5.09.
MS (ESI): m/z [M + H]+ calcd for C23H21O5: 377.14; found: 377.10.
Ethyl 3,4-Dihydroxy-9-methyl-7-(4-nitrophenyl)-6-oxo-7,8-di-
hydro-6H-dibenzo[b,d]pyran-8-carboxylate (4o)
Yellow solid; yield: 1.38 g (79%); mp 164–166 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.12 (s, 1 H), 9.39 (s, 1 H),
8.13 (d, J = 8.7 Hz, 2 H), 7.49 (d, J = 8.7 Hz, 2 H), 7.41 (d, J = 9.0
Hz, 1 H), 7.05 (s, 1 H), 6.87 (d, J = 9.0 Hz, 1 H), 4.76 (s, 1 H), 4.14–
4.04 (m, 2 H), 3.57 (s, 1 H), 2.04 (s, 3 H), 1.15 (t, J = 7.2 Hz, 3 H).
Anal. Calcd for C23H20O5: C, 73.39; H, 5.36. Found: C, 73.41; H,
5.29.
Ethyl 3,9-Dihydroxy-9-methyl-6-oxo-7-phenyl-7,8,9,10-tetra-
hydro-6H-dibenzo[b,d]pyran-8-carboxylate (3a)
White solid; yield: 0.331 g (21%); mp 245–248 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.42 (s, 1 H), 7.61 (d, J = 8.7
Hz, 1 H), 7.22–7.08 (m, 5 H), 6.82 (dd, J = 8.7, 2.1 Hz, 1 H), 6.67
(d, J = 2.1 Hz, 1 H), 4.70 (s, 1 H), 4.27 (d, J = 10.5 Hz, 1 H), 4.05–
3.92 (m, 2 H), 3.11 (dd, J = 18.3, 2.1 Hz, 1 H), 2.96 (d, J = 18.0 Hz,
13C NMR (75 MHz, DMSO-d6): δ = 170.4, 160.9, 150.0, 149.1,
147.0, 143.8, 143.7, 143.3, 133.0, 129.0, 124.2, 118.7, 115.4, 113.0,
112.1, 110.3, 61.5, 51.3, 39.0, 24.5, 14.4.
Synthesis 2012, 44, 2385–2395
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 6H-Dibenzo[b,d]pyran-6-ones
2393
MS (ESI): m/z [M + H]+ calcd for C23H20NO8: 438.12; found:
438.10.
13C NMR (75 MHz, DMSO-d6): δ = 167.3, 158.7, 151.6, 147.2,
146.8, 142.5, 141.7, 140.5, 136.8, 130.8, 130.4, 126.2, 124.6, 124.5,
122.9, 117.4, 116.4, 114.9, 61.6, 21.4, 20.2, 13.9.
Anal. Calcd for C23H19NO8: C, 63.16; H, 4.38; N, 3.20. Found: C,
63.09; H, 4.33; N, 3.17.
MS (ESI): m/z [M + H]+ calcd for C24H20NO6: 418.13; found:
418.10.
Ethyl 1,3-Dihydroxy-9-methyl-6-oxo-7-phenyl-7,8-dihydro-6H-
dibenzo[b,d]pyran-8-carboxylate (4p)
Yellow solid; yield: 0.989 g (63%); mp 177–180 °C.
Anal. Calcd for C24H19NO6: C, 69.06; H, 4.59; N, 3.36. Found: C,
69.11; H, 4.62; N, 3.38.
1H NMR (300 MHz, DMSO-d6): δ = 10.73 (s, 1 H), 10.30 (s, 1 H),
7.66 (s, 1 H), 7.26–7.15 (m, 5 H), 6.32 (d, J = 2.4 Hz, 1 H), 6.19 (d,
J = 2.4 Hz, 1 H), 4.58 (s, 1 H), 4.13–4.01 (m, 2 H), 3.36 (s, 1 H),
1.92 (s, 3 H), 1.14 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 170.9, 161.5, 161.1, 158.4,
158.1, 156.4, 155.4, 143.6, 141.3, 129.0, 127.5, 122.5, 112.1, 109.3,
100.1, 95.2, 61.3, 51.0, 38.8, 25.2, 14.4.
Ethyl 3-Methoxy-7,9-dimethyl-6-oxo-6H-dibenzo[b,d]pyran-8-
carboxylate (1c)
White solid; yield: 258 mg (79%); mp 149–151 °C.
1H NMR (300 MHz, DMSO-d6): δ = 8.18 (d, J = 8.7 Hz, 1 H), 8.08
(s, 1 H), 6.96–6.91 (m, 2 H), 4.39 (q, J = 7.2 Hz, 2 H), 3.85 (s, 3 H),
2.61 (s, 3 H), 2.38 (s, 3 H), 1.34 (t, J = 7.2 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 169.0, 162.0, 159.7, 152.8,
141.4, 139.3, 137.0, 136.2, 125.6, 121.7, 116.1, 112.7, 110.6, 101.2,
61.8, 56.3, 20.15, 20.11, 14.5.
MS (ESI): m/z [M + H]+ calcd for C23H21O6: 393.13; found: 393.10.
Anal. Calcd for C23H20O6: C, 70.40; H, 5.14. Found: C, 70.28; H,
5.11.
MS (ESI): m/z [M + H]+ calcd for C19H19O5: 327.12; found: 327.15.
Anal. Calcd for C19H18O5: C, 69.93; H, 5.56. Found: C, 70.04; H,
5.65.
Ethyl 1,3-Dihydroxy-9-methyl-7-(4-nitrophenyl)-6-oxo-7,8-di-
hydro-6H-dibenzo[b,d]pyran-8-carboxylate (4q)
Yellow solid; yield: 1.16 g (66%); mp 188–190 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.80 (s, 1 H), 10.36 (s, 1 H),
8.11 (d, J = 8.7 Hz, 2 H), 7.68 (s, 1 H), 7.46 (d, J = 8.7 Hz, 2 H),
6.34 (d, J = 2.4 Hz, 1 H), 6.21 (d, J = 2.4 Hz, 1 H), 4.72 (s, 1 H),
4.10–4.00 (m, 2 H), 3.46 (s, 1 H), 1.95 (s, 3 H), 1.15 (t, J = 7.2 Hz,
3 H).
13C NMR (75 MHz, DMSO-d6): δ = 170.5, 161.4, 160.8, 158.2,
156.6, 149.2, 147.0, 144.1, 141.4, 130.3, 129.1, 124.1, 122.6, 111.1,
100.1, 95.5, 61.4, 50.2, 38.7, 25.1, 14.4.
Ethyl 3-Methoxy-9-methyl-6-oxo-7-phenyl-6H-dibenzo[b,d]py-
ran-8-carboxylate (1d)
White solid; yield: 0.280 g (72%); mp 144–145 °C.
1H NMR (300 MHz, DMSO-d6): δ = 8.26 (s, 1 H), 8.25 (d, J = 9.3
Hz, 1 H), 7.35–7.32 (m, 3 H), 7.17–7.14 (m, 2 H), 6.96 (dd, J = 9.0,
2.4 Hz, 1 H), 6.90 (d, J = 2.7 Hz, 1 H), 3.87 (q, J = 6.9 Hz, 2 H),
3.83 (s, 3 H), 2.42 (s, 3 H), 0.84 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 167.7, 162.1, 158.5, 153.1,
142.8, 141.3, 139.3, 136.8, 136.3, 128.9, 127.7, 127.5, 125.7, 123.2,
115.4, 112.7, 110.6, 101.4, 61.2, 56.3, 20.1, 13.9.
MS (ESI): m/z [M + H]+ calcd for C23H20NO8: 438.12; found:
438.10.
MS (ESI): m/z [M + H]+ calcd for C24H21O5: 389.14; found: 389.10;
Anal. Calcd for C23H19NO8: C, 63.16; H, 4.38; N, 3.20. Found: C,
63.06; H, 4.34; N, 3.16.
m/z [2 M + Na]+ calcd for C48H40O10Na: 799.25; found: 799.25.
Anal. Calcd for C24H20O5: C, 74.21; H, 5.19. Found: C, 74.13; H,
5.25.
6H-Dibenzo[b,d]pyran-6-ones 1a–q; General Procedure
At 0 °C with stirring under N2, fresh distilled DBU (1.1 equiv) was
added to a soln of 4a–q (1.0 equiv) in anhyd MeCN (20 mL). Then,
BrCCl3 (1.1 equiv) was added dropwise via syringe over 10 min.
The mixture was allowed to warm to r.t. and stirred until the starting
material was completely consumed (TLC monitoring). The mixture
was neutralized with TFA (1.1 equiv), and the solvent was evapo-
rated in vacuo. The residue was purified by flash chromatography
to provide 1a–q.
Ethyl 3-Acetoxy-9-methyl-6-oxo-6H-dibenzo[b,d]pyran-8-car-
boxylate (1e)
White solid; yield: 0.218 g (64%); mp 204–206 °C.
1H NMR (300 MHz, DMSO-d6): δ = 8.58 (s, 1 H), 8.43 (d, J = 8.4
Hz, 1 H), 8.36 (s, 1 H), 7.29 (s, 1 H), 7.24 (dd, J = 8.4, 2.1 Hz, 1 H),
4.34 (q, J = 6.9 Hz, 2 H), 2.71 (s, 3 H), 2.31 (s, 3 H), 1.35 (t, J = 6.9
Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 169.3, 165.8, 160.0, 153.1,
152.4, 147.3, 136.9, 132.3, 130.4, 126.1, 125.8, 119.4, 118.7, 115.3,
111.5, 61.6, 22.2, 21.4, 14.6.
Ethyl 3,9-Dimethyl-6-oxo-7-phenyl-6H-dibenzo[b,d]pyran-8-
carboxylate (1a)
White solid; yield: 0.272 g (73%); mp 181–184 °C.
1H NMR (300 MHz, DMSO-d6): δ = 8.31 (s, 1 H), 8.20 (d, J = 8.4
Hz, 1 H), 7.35–7.29 (m, 3 H), 7.19–7.10 (m, 4 H), 3.88 (q, J = 6.9
Hz, 2 H), 2.43 (s, 3 H), 2.37 (s, 3 H), 0.84 (t, J = 6.9 Hz, 3 H).
MS (ESI): m/z [M + H]+ calcd for C19H17O6: 341.10; found: 341.05.
Anal. Calcd for C19H16O6: C, 67.05; H, 4.74. Found: C, 67.17; H,
4.71.
13C NMR (75 MHz, DMSO-d6): δ = 167.7, 158.4, 151.6, 142.7,
142.1, 141.3, 139.3, 136.5, 128.9, 127.7, 127.5, 125.9, 124.3, 123.6,
117.2, 116.4, 115.0, 61.2, 21.3, 20.1, 13.9.
Ethyl 3-Acetoxy-9-methyl-6-oxo-7-phenyl-6H-dibenzo[b,d]py-
ran-8-carboxylate (1f)
White solid; yield: 0.254 g (61%); mp 193–195 °C.
MS (ESI): m/z [M + H]+ calcd for C24H21O4: 373.14; found: 373.10.
1H NMR (300 MHz, CDCl3): δ = 8.54 (d, J = 9.6 Hz, 1 H), 7.40–
7.37 (m, 3 H), 7.27–7.23 (m, 2 H), 7.12 (s, 1 H), 7.11–7.08 (m, 2 H),
3.94 (q, J = 7.2 Hz, 2 H), 2.52 (s, 3 H), 2.34 (s, 3 H), 0.95 (t, J = 7.2
Hz, 3 H).
Anal. Calcd for C24H20O4: C, 77.40; H, 5.41. Found: C, 77.29; H,
5.36.
13C NMR (75 MHz, CDCl3): δ = 168.7, 167.1, 157.7, 152.1, 145.0,
141.4, 138.5, 138.3, 135.2, 129.6, 129.0, 128.4, 127.7, 127.6, 127.2,
118.1, 117.9, 114.2, 110.9, 61.6, 21.2, 14.6, 13.7.
Ethyl 3,9-Dimethyl-7-(4-nitrophenyl)-6-oxo-6H-diben-
zo[b,d]pyran-8-carboxylate (1b)
White solid; yield: 0.313 g (75%); mp 205–208 °C.
1H NMR (300 MHz, DMSO-d6): δ = 8.45 (s, 1 H), 8.28 (d, J = 8.1
Hz, 1 H), 8.23 (d, J = 8.7 Hz, 2 H), 7.47 (d, J = 8.7 Hz, 2 H), 7.23
(d, J = 8.1 Hz, 1 H), 7.18 (s, 1 H), 3.91 (q, J = 7.2 Hz, 2 H), 2.46 (s,
3 H), 2.40 (s, 3 H), 0.87 (t, J = 7.2 Hz, 3 H).
MS (ESI): m/z [M + H]+ calcd for C25H21O6: 417.13; found: 417.10.
Anal. Calcd for C25H20O6: C, 72.11; H, 4.84. Found: C, 72.09; H,
4.92.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2385–2395

2394
C.-Y. Chen et al.
PAPER
Ethyl 3-Acetoxy-9-methyl-7-(4-nitrophenyl)-6-oxo-6H-diben-
zo[b,d]pyran-8-carboxylate (1g)
White solid; yield: 0.309 g (67%); mp 239–241 °C.
13C NMR (75 MHz, DMSO-d6): δ = 167.8, 160.8, 158.6, 153.1,
142.8, 141.3, 139.4, 137.1, 135.9, 128.8, 127.7, 127.5, 125.9, 122.9,
115.1, 113.5, 109.4, 102.9, 61.2, 20.2, 13.9.
1H NMR (300 MHz, CDCl3): δ = 8.27 (d, J = 8.4 Hz, 2 H), 8.11 (d,
J = 8.4 Hz, 1 H), 8.04 (s, 1 H), 7.42 (d, J = 8.4 Hz, 2 H), 7.17–7.12
(m, 2 H), 3.99 (q, J = 7.2 Hz, 2 H), 2.56 (s, 3 H), 2.35 (s, 3 H), 1.00
(t, J = 7.2 Hz, 3 H).
MS (ESI): m/z [M – H]– calcd for C23H17O5: 373.11; found: 373.10.
Anal. Calcd for C23H18O5: C, 73.79; H, 4.85. Found: C, 73.81; H,
4.87.
13C NMR (75 MHz, CDCl3): δ = 168.8, 167.2, 158.4, 152.7, 152.2,
147.3, 145.9, 142.1, 141.2, 136.7, 136.2, 129.5, 124.2, 123.6, 122.9,
118.5, 116.3, 114.9, 111.0, 61.7, 21.1, 20.6, 13.8.
MS (ESI): m/z [M + H]+ calcd for C25H20NO8: 462.12; found:
462.10.
Ethyl 3-Hydroxy-9-methyl-7-(4-methylphenyl)-6-oxo-6H-
dibenzo[b,d]pyran-8-carboxylate (1l)
White solid; yield: 0.268 g (69%); mp 206–208 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.40 (s, 1 H), 8.24 (s, 1 H),
8.20 (d, J = 8.7 Hz, 1 H), 7.14 (d, J = 7.8 Hz, 2 H), 7.02 (d, J = 7.8
Hz, 2 H), 6.84 (dd, J = 8.7, 2.4 Hz, 1 H), 6.68 (d, J = 2.4 Hz, 1 H),
3.89 (q, J = 7.2 Hz, 2 H), 2.42 (s, 3 H), 2.34 (s, 3 H), 0.87 (t, J = 7.2
Hz, 3 H).
Anal. Calcd for C25H19NO8: C, 65.07; H, 4.15; N, 3.04. Found: C,
65.12; H, 4.19; N, 3.07.
Ethyl 1,3,9-Trimethyl-6-oxo-7-phenyl-6H-dibenzo[b,d]pyran-
8-carboxylate (1h)
White solid; yield: 0.247 g (64%); mp 170–173 °C.
13C NMR (75 MHz, DMSO-d6): δ = 167.9, 160.8, 158.6, 153.1,
142.9, 141.2, 137.2, 136.6, 136.5, 136.1, 128.7, 128.3, 126.0, 122.8,
115.2, 113.5, 109.4, 102.9, 61.2, 21.4, 20.2, 13.9.
1H NMR (300 MHz, CDCl3): δ = 7.92 (s, 1 H), 7.21–7.08 (m, 7 H),
4.01 (q, J = 6.9 Hz, 2 H), 2.51 (s, 3 H), 2.43 (s, 3 H), 2.39 (s, 3 H),
1.00 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 168.9, 160.1, 151.4, 143.9, 142.1,
141.5, 137.2, 136.9, 136.8, 135.7, 128.4, 128.2, 125.8, 123.0, 122.3,
117.5, 116.2, 114.8, 61.7, 21.4, 21.3, 20.4, 13.6.
MS (ESI): m/z [M – H]– calcd for C24H19O5: 387.12; found: 387.10.
Anal. Calcd for C24H20O5: C, 74.21; H, 5.19. Found: C, 74.12; H,
5.21.
Ethyl 3-Hydroxy-9-methyl-7-(4-nitrophenyl)-6-oxo-6H-diben-
zo[b,d]pyran-8-carboxylate (1m)
White solid; yield: 0.315 g (75%); mp >270 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.47 (s, 1 H), 8.28–8.18 (m,
4 H), 7.45 (d, J = 7.8 Hz, 2 H), 6.84 (d, J = 7.8 Hz, 1 H), 6.67 (s, 1
H), 3.89 (q, J = 6.9 Hz, 2 H), 2.43 (s, 3 H), 0.85 (t, J = 6.9 Hz, 3 H).
MS (ESI): m/z [M + H]+ calcd for C25H23O4: 387.16; found: 387.20.
Anal. Calcd for C25H22O4: C, 77.70; H, 5.74. Found: C, 77.64; H,
5.68.
Ethyl 3-Hydroxy-9-methyl-6-oxo-6H-dibenzo[b,d]pyran-8-car-
boxylate (1i)
White solid; yield: 0.215 g (72%); mp 260–263 °C.
13C NMR (75 MHz, DMSO-d6): δ = 167.4, 158.9, 149.1, 148.1,
147.2, 147.1, 141.9, 141.5, 140.5, 138.0, 135.0, 132.9, 130.4, 124.1,
122.9, 114.7, 112.9, 110.1, 61.6, 20.2, 13.9.
1H NMR (300 MHz, DMSO-d6): δ = 10.46 (s, 1 H), 8.43 (s, 1 H),
8.05 (d, J = 8.7 Hz, 1 H), 8.00 (s, 1 H), 6.79 (dd, J = 9.0, 2.4 Hz, 1
H), 6.66 (d, J = 2.4 Hz, 1 H), 4.28 (q, J = 7.2 Hz, 2 H), 2.61 (s, 3 H),
1.34 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 165.5, 161.2, 160.2, 153.3,
147.0, 137.7, 132.4, 128.1, 125.7, 124.6, 116.9, 113.6, 108.8, 103.3,
61.2, 22.4, 14.5.
MS (ESI): m/z [M – H]– calcd for C23H16NO7: 418.09; found:
418.05.
Anal. Calcd for C23H17NO7: C, 65.87; H, 4.09; N, 3.34. Found: C,
65.93; H, 4.18; N, 3.36.
Ethyl 3,4-Dihydroxy-9-methyl-6-oxo-7-phenyl-6H-diben-
zo[b,d]pyran-8-carboxylate (1n)
White solid; yield: 0.199 g (51%); mp 186–189 °C.
MS (ESI): m/z [M – H]– calcd for C17H13O5: 297.08; found: 297.05.
1H NMR (300 MHz, DMSO-d6): δ = 10.46 (s, 1 H), 10.38 (s, 1 H),
8.24 (s, 1 H), 8.19 (d, J = 9.0 Hz, 1 H), 7.36–7.29 (m, 3 H), 7.18–
7.12 (m, 2 H), 6.84 (d, J = 9.0 Hz, 1 H), 4.01 (q, J = 7.5 Hz, 2 H),
2.41 (s, 3 H), 1.16 (t, J = 7.5 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 167.8, 159.5, 159.0, 152.5,
151.6, 140.1, 136.7, 134.2, 130.6, 129.3, 128.7, 127.5, 127.1, 125.9,
117.1, 112.7, 109.7, 102.7, 61.2, 15.1, 13.9.
Anal. Calcd for C17H14O5: C, 68.45; H, 4.73. Found: C, 68.54; H,
4.83.
Ethyl 3-Hydroxy-7,9-dimethyl-6-oxo-6H-dibenzo[b,d]pyran-8-
carboxylate (1j)
White solid; yield: 0.237 g (76%); mp 210–213 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.47 (s, 1 H), 7.87 (d, J = 9.0
Hz, 1 H), 6.95 (s, 1 H), 6.72 (d, J = 9.0 Hz, 1 H), 5.92 (s, 1 H), 4.20
(q, J = 7.2, Hz, 2 H), 2.23 (s, 3 H), 2.07 (s, 3 H), 1.25 (t, J = 7.2 Hz,
3 H).
13C NMR (75 MHz, DMSO-d6): δ = 169.4, 162.6, 159.1, 153.0,
141.0, 139.7, 137.5, 136.4, 126.1, 121.3, 116.5, 112.2, 111.0, 101.2,
61.8, 20.15, 20.11, 14.5.
MS (ESI): m/z [M – H]– calcd for C23H17O6: 389.10; found: 389.05.
Anal. Calcd for C23H18O6: C, 70.76; H, 4.65. Found: C, 70.64; H,
4.61.
Ethyl 3,4-Dihydroxy-9-methyl-7-(4-nitrophenyl)-6-oxo-6H-
dibenzo[b,d]pyran-8-carboxylate (1o)
White solid; yield: 0.235 g (54%); mp 159–162 °C.
MS (ESI): m/z [M + H]+ calcd for C18H17O5: 313.11; found: 313.10.
1H NMR (300 MHz, DMSO-d6): δ = 10.00 (s, 1 H), 9.26 (s, 1 H),
8.31 (s, 1 H), 8.24 (d, J = 9.0 Hz, 2 H), 7.72 (d, J = 9.0 Hz, 1 H),
7.49 (d, J = 9.0 Hz, 2 H), 6.87 (d, J = 9.0 Hz, 1 H), 3.91 (q, J = 6.9
Hz, 2 H), 2.45 (s, 3 H), 0.87 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 167.4, 158.9, 149.1, 147.1,
141.9, 141.5, 140.6, 139.6, 138.0, 135.0, 132.9, 130.4, 124.1, 122.9,
115.0, 114.7, 113.0, 110.1, 61.6, 20.2, 13.9.
Anal. Calcd for C18H16O5: C, 69.22; H, 5.16. Found: C, 69.28; H,
5.19.
Ethyl 3-Hydroxy-9-methyl-6-oxo-7-phenyl-6H-dibenzo[b,d]py-
ran-8-carboxylate (1k)
White solid; yield: 0.270 g (72%); mp 192–195 °C.
1H NMR (300 MHz, DMSO-d6): δ = 10.39 (s, 1 H), 8.24 (s, 1 H),
8.20 (d, J = 9.0 Hz, 1 H), 7.35–7.31 (m, 3 H), 7.16–7.13 (m, 2 H),
6.84 (dd, J = 9.0, 2.4 Hz, 1 H), 6.67 (d, J = 2.4 Hz, 1 H), 3.87 (q, J =
6.9 Hz, 2 H), 2.42 (s, 3 H), 0.84 (t, J = 6.9 Hz, 3 H).
MS (ESI): m/z [M – H]– calcd for C23H16NO8: 434.09; found:
434.05.
Synthesis 2012, 44, 2385–2395
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 6H-Dibenzo[b,d]pyran-6-ones
2395
Anal. Calcd for C23H17NO8: C, 63.45; H, 3.94; N, 3.22. Found: C,
63.36; H, 3.89; N, 3.16.
883. (d) Altemöller, M.; Gehring, T.; Cudaj, J.; Podlech, J.;
Goesmann, H.; Feldmann, C.; Rothenberger, A. Eur. J. Org.
Chem. 2009, 2130.
Ethyl 1,3-Dihydroxy-9-methyl-6-oxo-7-phenyl-6H-diben-
zo[b,d]pyran-8-carboxylate (1p)
White solid; yield: 0.203 g (52%); mp 220–222 °C.
(3) (a) Cordero-Vargas, A.; Quiclet-Sire, B.; Zard, S. Z. Org.
Biomol. Chem. 2005, 3, 4432. (b) Takemura, I.; Imura, K.;
Matsumoto, T.; Suzuki, K. Org. Lett. 2004, 6, 2503.
(c) James, C. A.; Snieckus, V. J. Org. Chem. 2009, 74, 4080.
(d) Pottie, I. R.; Nandaluru, P. R.; Benoit, W. L.; Miller, D.
O.; Dawe, L. N.; Bodwell, G. J. J. Org. Chem. 2011, 76,
9015. (e) Madan, S.; Cheng, C. H. J. Org. Chem. 2006, 71,
8312.
1H NMR (300 MHz, DMSO-d6): δ = 10.16 (s, 1 H), 9.44 (s, 1 H),
7.71 (s, 1 H), 7.33–7.25 (m, 3 H), 7.14–7.09 (m, 2 H), 6.88 (s, 1 H),
6.62 (s, 1 H), 3.95 (q, J = 7.2 Hz, 2 H), 2.21 (s, 3 H), 1.03 (t, J = 7.2
Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 168.2, 159.8, 158.2, 155.3,
153.5, 148.7, 147.2, 137.0, 131.7, 130.4, 129.1, 125.8, 123.7, 117.7,
101.4, 98.6, 95.0, 93.6, 61.4, 16.8, 14.3.
(4) Findlay, J. A.; Daljeet, A.; Murray, P. J.; Rej, R. N. Can. J.
Chem. 1987, 65, 427.
(5) (a) Pandey, J.; Jha, A. K.; Hajela, K. Bioorg. Med. Chem.
2004, 12, 2239. (b) Teske, J. A.; Dieters, A. Org. Lett. 2008,
10, 2195.
(6) (a) Darbarwar, M.; Sundaramurthy, V. Synthesis 1982, 337.
(b) Kawasaki, T.; Yamamoto, Y. J. Org. Chem. 2002, 67,
5138; and references cited therein.
MS (ESI): m/z [M – H]– calcd for C23H17O6: 389.10; found: 389.05.
Anal. Calcd for C23H18O6: C, 70.76; H, 4.65. Found: C, 70.67; H,
4.71.
Ethyl 1,3-Dihydroxy-9-methyl-7-(4-nitrophenyl)-6-oxo-6H-
dibenzo[b,d]pyran-8-carboxylate (1q)
White solid; yield: 0.209 g (48%); mp 194–196 °C.
(7) (a) Sawada, K.; Hirai, H.; Golden, P.; Okada, S.; Sawada,
Y.; Hashimoto, M.; Tanaka, H. Chem. Pharm. Bull. 1998,
46, 1683. (b) Pisani, L.; Catto, M.; Giangreco, I.; Leonetti,
F.; Nicolotti, O.; Stefanachi, A.; Cellamare, S.; Carotti, A.
ChemMedChem 2010, 5, 1616. (c) Chebaane, K.; Guyot,
M.; Molho, D. Bull. Soc. Chim. Fr. 1975, 2521. (d) McGee,
L. R.; Confalone, P. N. J. Org. Chem. 1988, 53, 3695.
(e) Hua, D. H.; Saha, S.; Roche, D.; Maeng, J. C.; Iguchi, S.;
Baldwin, C. J. Org. Chem. 1992, 57, 399. (f) Kwok, D.-I.;
Outten, R. A.; Huhn, R.; Daves, G. D. Jr. J. Org. Chem.
1988, 53, 5359. (g) Guillaumet, G.; Hretani, M.; Coudert,
G.; Averbeck, D.; Averbeck, S. Eur. J. Med. Chem. 1990,
25, 45. (h) Bovy, P. R.; Collins, J. T.; McMahon, E. G.;
Hutton, W. C. J. Med. Chem. 1991, 34, 2410. (i) Outten, R.
A.; Daves, G. D. Jr. J. Org. Chem. 1989, 54, 29. (j) Santana,
L.; González-Díaz, H.; Quezada, E.; Uriarte, E.; Yáñez, M.;
Viña, D.; Orallo, F. J. Med. Chem. 2008, 51, 6740.
(8) Metwally, M. A.; Khalil, A. M. J. Indian Chem. Soc. 1988,
65, 766; 1H NMR and 13C NMR of the two coumarin-fused
2-cyclohexadienes were not determined in this paper.
(9) (a) Pandiarajan, K.; Sabapathy, Mohan. R. T.; Gomathi, R.;
Muthukumaran, G. Magn. Reson. Chem. 2005, 43, 430.
(b) Srinivasan, M.; Perumal, S. Tetrahedron 2006, 62, 7726.
(c) Blatt, A. H. Org. Synth. Coll. Vol. II; John Wiley & Sons:
London, 1969, 215. (d) Horning, E. C.; Denekas, M. O.;
Field, R. E. J. Org. Chem. 1944, 9, 547.
1H NMR (300 MHz, DMSO-d6): δ = 10.23 (s, 1 H), 9.30 (s, 1 H),
8.19 (d, J = 8.7 Hz, 2 H), 7.63 (s, 1 H), 7.42 (d, J = 8.7 Hz, 2 H),
6.39 (d, J = 2.7 Hz, 1 H), 6.24 (d, J = 2.7 Hz, 1 H), 3.89 (q, J = 6.9
Hz, 2 H), 2.24 (s, 3 H), 0.87 (t, J = 6.9 Hz, 3 H).
13C NMR (75 MHz, DMSO-d6): δ = 167.8, 160.1, 159.4, 155.8,
153.0, 148.3, 146.7, 135.7, 130.9, 129.9, 129.4, 124.9, 122.8, 117.3,
100.9, 99.6, 95.6, 94.5, 61.4, 15.2, 13.9.
MS (ESI): m/z [M – H]– calcd for C23H16NO8: 434.09; found:
434.05.
Anal. Calcd for C23H17NO8: C, 63.45; H, 3.94; N, 3.22. Found: C,
63.41; H, 4.01; N, 3.19.
Crystallographic Details of 4k and 1l
CCDC-868312 (4k) and CCDC-868313 (1l) contain all crystallo-
graphic details of this publication and are available free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from
the following address: Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; or
email: deposit@ccdc.cam.ac.uk.
Acknowledgment
Financial supports from National Natural Science Foundation of
China (No. 20872059 and 21072091) and MOST of China (973 pro-
gram 2011CB808600) are gratefully acknowledged.
(10) Kitamura, T.; Yamamoto, K.; Kotani, M.; Oyamada, J.; Jia,
C.; Fujiwara, Y. Bull. Chem. Soc. Jpn. 2003, 76, 1889.
(11) Prajapati, D.; Gohain, M. Catal. Lett. 2007, 119, 59.
(12) (a) Bose, D. S.; Rudradas, A. P.; Hari Babu, M. Tetrahedron
Lett. 2002, 43, 9195. (b) Potdar, M. K.; Mohile, S. S.;
Salunkhe, M. M. Tetrahedron Lett. 2001, 42, 9285.
(c) Maheswara, M.; Siddaiah, V.; Lakishmi, G.; Damu, V.;
Rao, Y. K.; Rao, C. V. J. Mol. Catal. A: Chem. 2006, 255,
49.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2385–2395