A facile one-pot access to dibenzo[b,e]oxepines by a lewis acid catalysed tandem reaction

Article abstract of DOI:10.1002/ejoc.201001739

Dibenzo[b,e]oxepine derivatives have been constructed efficiently by one-pot tandem carbon-carbon bond formation reactions. First, 2-(3,5-dimethoxybenzyloxy)benzaldehydes were treated with various nucleophiles under I₂ catalysis and then 1-(3,5

Full text of DOI:10.1002/ejoc.201001739

FULL PAPER
DOI: 10.1002/ejoc.201001739
A Facile One-Pot Access to Dibenzo[b,e]oxepines by a Lewis Acid Catalysed
Tandem Reaction
Chada R. Reddy,*[a] Palacherla Ramesh,[a] Nagavaram N. Rao,[a] and Saiyed A. Ali[b]
Keywords: Heterocycles / Tandem reactions / Alkylation / Iodine / Lewis acid catalysis
Dibenzo[b,e]oxepine derivatives have been constructed ef-
ficiently by one-pot tandem carbon–carbon bond formation
reactions. First, 2-(3,5-dimethoxybenzyloxy)benzaldehydes
were treated with various nucleophiles under I2 catalysis and
then
1-(3,5-dimethoxybenzyloxy)-3,5-dimethoxybenzene
was treated with several aromatic as well as heteroaromatic
aldehydes under BF3·Et2O catalytic conditions to provide di-
benzo[b,e]oxepines in good yields.
Introduction
Dibenzoxepine is an important structural motif in vari-
ous pharmaceuticals with remarkable diverse biological ac-
tivities.[1] For instance, Doxepine, a dibenzoxepine tricyclic
compound, is most commonly used orally as an anti-de-
pressant[2] and Olopatadine, an anti-histamine, anti-cholin-
ergic and mast cell stabilizer, is used to treat the symptoms
of allergic pink eye (Figure 1).[3] Dibenzoxepines have also
been used as inhibitors of acyl-CoA, anti-allergic agents
and non-prostenoid thrombaxane A2 receptor antago-
nists.[4] In addition, these scaffolds are found in bioactive
natural products.[5] As a result of their importance, dibenz-
oxepines are synthetic targets of many researchers. The fa-
miliar approaches to synthesizing the dibenzoxepine ring
system are the palladium-catalysed cascade carbometall-
ation/cross-coupling of alkynes, preparation of the 11-oxo
scaffold followed by Wittig reaction or dehydration of carb-
inols and others.[6,7] Most of these methods provide di-
benzo[b,e]oxepine compounds containing an exocyclic ole-
fin substitution at the C-11 carbon. Thus, development of
efficient methods for the synthesis of dibenzoxepines with
various functional groups is highly desirable.
Figure 1. Structures of doxepine and olopatadine.
ylation of tosylhydrazones and the alkylation of 1,3-dicarb-
onyl compounds to give various oxygenated heterocycles
have been successfully demonstrated.[8] To further extend
the use of benzylic alcohols, in particular, by generating
them in situ, we became interested in the synthesis of di-
benzoxepine derivatives. This was envisioned by a cascade
sequence of nucleophilic addition to (benzyloxy)benzalde-
hyde/intramolecular Friedel–Crafts alkylation or vice versa
to give the 6,11-dihydrodibenzoxepine derivative
(Scheme 1). To the best of our knowledge there are no such
one-pot methods available for the synthesis of dibenzoxep-
ines. While this work was in progress, two papers appeared
reporting a similar concept for the synthesis of xanthenes
and in one of the reports a single example of dibenzoxepine
was achieved in 48% yield using a different substrate.[9]
Furthermore, the synthesis of 6,11-dihydrodibenzoxepines
is much less studied.[4c,10] The above observations combined
with our interest prompted us to explore a one-pot tandem
Our recent studies have focused on the use of benzylic/
propargylic alcohols as alkylating agents in carbon–carbon,
carbon–nitrogen and carbon–oxygen bond-forming reac-
tions for the synthesis of heterocyclic compounds. For ex-
ample, the C-3 alkylation of 4-hydroxycoumarin to yield
furanocoumarins, the synthesis of pyrazoles by the N-alk-
[a] Organic Division-I (NPL),
Indian Institute of Chemical Technology,
Hyderabad 500 607, India
Fax: +91-040-27160512
E-mail: rajireddy@iict.res.in
[b] National Institute of Pharmaceutical Education and Research,
Hyderabad 500 037, India
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001739.
Scheme 1. Proposed cascade sequence.
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reaction towards 6,11-dihydrodibenzoxepines and the re- tion. To ensure this, we prepared 2-(3,5-dimethoxy-
sults are described in this paper.
benzyloxy)benzaldehyde (1b) by the O-benzylation of sali-
cylaldehyde using 3,5-dimethoxybenzyl bromide/K2CO3 in
DMF. The reaction of 1b was first studied with N-methylin-
dole (2a) in the presence of BF3·Et2O (10 mol-%) in dichlo-
romethane at room temp. The cyclized product, dibenzoxe-
pine derivative 3ba, was obtained in 65% yield (entry 7,
Table 1). When the reaction temperature was raised to re-
flux, there was no improvement in yield. Encouraged by the
above result, to optimize the reaction conditions, the reac-
tion of 1b with 2a was carried out in the presence of various
acid catalysts such as FeCl3, B(C6F5)3, molecular iodine,
pTSA and AuCl3. Among the acid catalysts screened,
10 mol-% of molecular iodine provided 67% yield of 3ba
whereas the other catalysts afforded the product in lower
yields (entries 8–12, Table 1). However, changing the sol-
vent from CH2Cl2 to CH3CN facilitated an improvement in
the yield to 84% in the case of 10 mol-% I2, but no improve-
ment in yield was observed for BF3·E2O, pTSA or AuCl3
(entries 13–16, Table 1).
Results and Discussion
Initially we investigated the possibility of a one-pot tan-
dem nucleophilic addition/Friedel–Crafts cyclization on 2-
(benzyloxy)benzaldehyde (1a), which was easily obtained by
the O-benzylation of salicylaldehyde using benzyl bromide/
K2CO3 in DMF. The reaction of 1a was carried out with
N-methylindole (2a) in the presence of BF3·Et2O (10 mol-%)
in dichloromethane at room temperature. However, the
reaction did not give the expected dibenzoxepine 3aa, in-
stead triarylmethane 3a was obtained in 46% yield (entry 1,
Table 1). The same reaction using other acid catalysts such
as FeCl3, B(C6F5)3, molecular iodine and pTSA in dichloro-
methane also provided 3a (entries 2–5, Table 1). As gold
catalysts are gaining prominence,[11] we also tested the one-
pot tandem reaction using AuCl3 (entry 6, Table 1). These
results clearly demonstrate that, after the initial nucleophilic
addition of N-methylindole to 1a, no intramolecular cycli-
zation takes place, instead 3a obtained by SN1 nucleophilic
substitution with 2a. This may be due to the less nucleo-
philic nature of the phenyl ring present in the benzyl group.
Subsequently, we thought that a more electron-rich sub-
strate may be better suited for the proposed tandem reac-
Having demonstrated the viability of this catalytic strat-
egy in obtaining 3ba, we next explored the scope of the
transformation under the optimized conditions (10 mol-%
of I2, CH3CN, room temp.). Thus, the reaction of aldehyde
1b with several nucleophiles was studied and the results are
summarized in Table 2. Various electron-rich aromatics
Table 1. Optimization of the conditions for the reactions of 1a and 1b with 2a.[a]
[a] Reactions were carried out under N2 with 10 mol-% catalyst at room temp. [b] Isolated yields based on 1a or 1b used.
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Dibenzo[b,e]oxepines by Tandem Reaction
Table 2. Synthesis of 11-substituted dibenzo[b,e]oxepines by iodine-catalysed tandem cyclization.
[a] Isolated yields.
such as 1,3,5-trimethoxybenzene (2b), phenol (2c), indole vide the corresponding 11-substituted dibenzo[b,e]oxepines
(2d) and 2-phenylindole (2e) served as nucleophiles to pro- 3bb–be in good yields of between 67 and 80% (entries 1–
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4, Table 2). In addition, 1,3-dicarbonyl compounds such as dimethoxyphenol with 3,5-dimethoxybenzyl bromide. Once
acetylacetone (2f), 1,3-cyclohexanedione (2g) and 4-hy- the benzyl ethers 4a and 4b were in hand, we focused our
droxycoumarin (2h) are also found to be well suited for this attention on studying their reactivity with benzaldehyde to
I2-catalysed tandem reaction, giving the corresponding obtain the desired products. As presented in Table 3, when
products 3bf, 3bg and 3bh in 74, 76 and 88% yields, respec- 1,3-dimethoxy-5-(phenoxymethyl)benzene (4a) and benzal-
tively (entries 5–7, Table 2). Note that allyltrimethylsilane dehyde (5a) in I2 (10 mol-%) and acetonitrile were allowed
was successfully used as a nucleophile to obtain 11-allyldi- to react at room temp. for 12 h, a complex inseparable mix-
benzoxepine (3bi) in 64% yield (entry 8, Table 2). To further ture of products along with the starting material were ob-
expand the range of substrates, we decided to use bromo- tained, showing the reaction is not clean (entry 1, Table 3).
substituted benzyloxybenzaldehyde 1c, which will be useful However, the strongly electron-rich substrate 1-(3,5-di-
for preparing further analogues by palladium coupling re- methoxybenzyloxy)-3,5-dimethoxybenzene (4b) provided
actions. Accordingly, aldehyde 1c was treated with N-meth- 1,3,8,10-tetramethoxy-11-phenyl-6,11-dihydrodibenzo[b,e]-
ylindole (2a) under I2 catalysis to yield (76%) the dibenzo- oxepine (6ba) in 71% yield in 6 h (entry 2, Table 3).
xepine 3ca in 6 h (entry 9, Table 2). The reaction of 1c with
1,3,5-trimethoxybenzene (2b), phenol (2c) and indole (2d)
furnished the corresponding products 3cb, 3cc and 3cd in
67, 64 and 73% yields, respectively (entries 10–12, Table 2).
Table 4. Synthesis of 11-substituted dibenzo[b,e]oxepines by
BF3·Et2O-catalysed tandem cyclization.
Finally, a different substrate 1d, derived from salicylalde-
hyde and 3,5-dimethoxybenzoic acid, was also tested; 1d
underwent the cascade cyclization reaction with 1,3,5-tri-
methoxybenzene (2b) to afford the 11-substituted di-
benzo[b,e]oxepin-6(11H)-one 3db in 52% yield (Scheme 2).
Scheme 2. Reaction of 1d of 1,3,5-trimethoxybenzene.
In addition, we were interested in knowing whether a
benzyl ether and an external aldehyde could be used as sub-
strates to prepare similar 11-substituted dibenzo[b,e]oxepine
derivatives. For this reason, two different benzyl ethers 4a
and 4b were prepared by the alkylation of phenol and 3,5-
Table 3. Optimization of the conditions for the reactions of 4a and
4b with 5a.[a]
[a] Reactions were carried out under N2 with 10 mol-% catalyst at
room temp. [b] Isolated yields based on 4a or 4b used.
[a] Isolated yield.
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Dibenzo[b,e]oxepines by Tandem Reaction
Furthermore, we examined the reaction of 4b with 5a under with 3bi after 1 h. The intermediate 8 was converted into
different conditions to check for improvements in the yield 3bi under the same reactions conditions (Scheme 4).[13] The
of the desired product. Catalysts such as pTSA, BF3·Et2O mechanism was further supported by the reaction of 1b in
and ZnCl2 in CH3CN provided similar results to those ob- I2/CH3CN in the absence of a nucleophile, which did not
tained with I2/CH3CN (entries 3–5, Table 3), but AuCl3 proceed to give the expected 7 (Scheme 4).
provided a low yield of the product (entry 6, Table 3). Inter-
estingly, the reaction of 4b with 5a was complete in 1 h with
BF3·Et2O in CH2Cl2, with 6ba obtained in 84% yield (en-
try 6, Table 3).
Under the above optimized conditions, we then focused
on the reaction of various aldehydes with 4b. As indicated
in Table 4, benzaldehydes with electron-donating and -with-
drawing groups 5b–5e underwent successful cascade reac-
tions to furnish the corresponding 11-aryldibenzo[b,e]oxep-
ines 6bb–6be in good yields of between 70 and 80% (en-
tries 1–4, Table 4). Similarly, heterocyclic aldehydes such as
thiophene-2-carbaldehyde (5f), N-tosylindole-3-carbal-
dehyde (5g), chromenecarbaldehyde 5h and pyrazolecarbal-
dehyde 5i also reacted well with 4b to give the products 6bf–
Scheme 4. Reactions of 1b.
6bi in yields of 65, 90, 92 and 72%, respectively (entries 5–
8, Table 4). Reaction of trans-cinnamaldehyde (5j) with 4b
in BF3·Et2O/CH2Cl2 at room temp. afforded 6bj in 60%
yield (entry 9, Table 4). However, an aliphatic aldehyde,
Conclusions
We have developed a facile method for the synthesis of
11-substituted dibenzoxepine derivatives. The method in-
volves an acid-catalysed tandem nucleophilic addition/Frie-
del–Crafts-type cyclization reaction. Two different strate-
gies have been demonstrated: 1) the reaction of O-(benz-
yloxy)salicylaldehyde with various nucleophiles under I2 ca-
talysis and 2) the reaction of O-(benzyloxy)phenol with aro-
matic aldehydes by BF3·Et2O catalysis. The method requires
10 mol-% of inexpensive I2 or BF3·Et2O to obtain the de-
sired products in good yields. Furthermore, the mild reac-
tion conditions and operational simplicity render this ap-
proach an interesting method. Although there are a few
limitations regarding the substrates, this method opens up
a new approach to accessing dibenzoxepine derivatives.
heptanal (5k), did not participate in the reaction with 4b
even at higher temperatures (entry 10, Table 4). This dem-
onstrates that the developed protocol is suitable only for
aromatic aldehydes and a completely electron-rich sub-
strate.
A plausible reaction mechanism is shown in Scheme 3.
Mechanistically, it is conceivable that the reaction involves
the initial formation of intermediate alcohol A by the ad-
dition of a nucleophile to the aldehyde and a subsequent
intramolecular Friedel–Crafts-type cyclization of A via the
formation of benzylic carbocation B in the presence of an
iodine catalyst.[12] The reactions of 1b with nucleophiles 2a–
i provided directly the products 3ba–bi without isolation of
any intermediates. However, from the reaction of 1b with 2i
in BF3·Et2O/CH2Cl2, the intermediate 8 was isolated along
Experimental Section
General: 1H and 13C NMR spectra were recorded in CDCl3 on
300, 500 or 75 MHz spectrometers at ambient temperature. The
chemical shifts (δ) are reported in ppm downfield from TMS as
internal standard and signal patterns are indicated as follows: s,
singlet; d, doublet; dd, doublet of doublet; td, triplet of doublet; t,
triplet; m, multiplet; br. s, broad singlet. The coupling constants
(J) are given in Hz. The FTIR spectra were recorded as KBr thin
films or neat. For low (MS) and high (HRMS) resolution mass
spectrometry, m/z ratios are reported as atomic mass units. All the
reagents and solvents were reagent grade and used without further
purification unless specified otherwise. Technical grade ethyl acet-
ate and petroleum ether used for column chromatography were dis-
tilled prior to use. Column chromatography was carried out by
using silica gel (60–120 mesh) packed in glass columns. All the reac-
tions were performed under nitrogen in flame- or oven-dried glass-
ware with magnetic stirring.
General Procedure for the Preparation of 11-Substituted Dibenzo-
[b,e]oxepines 3ba–3bi, 3ca–3cd and 3db: The appropriate nucleo-
phile (1 mmol) was added to a solution of O-benzyloxysalicylal-
Scheme 3. Proposed mechanism for the iodine-mediated cyclization
of 1b.
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C. R. Reddy, P. Ramesh, N. N. Rao, S. A. Ali
FULL PAPER
dehyde 1b, 1c or 1d (1 mmol) in CH3CN (5 mL), followed by mo-
lecular iodine (10 mol-%). The resulting mixture was stirred at
room temp. for the given time (Table 2) under nitrogen. After com-
pletion of the reaction, the mixture was quenched with water
NMR (300 MHz, CDCl3): δ = 8.13 (s, 1 H, NH), 7.54 (d, J =
7.3 Hz, 2 H, Ar), 7.36 (t, J = 7.3 Hz, 2 H, Ar), 7.24 (t, J = 6.6 Hz,
2 H, Ar), 7.19–7.07 (m, 3 H, Ar), 6.94–6.76 (m, 3 H, Ar), 6.63 (s,
1 H, Ar), 6.50 (d, J = 2.2 Hz, 1 H, Ar), 6.35 (d, J = 2.1 Hz, 1 H,
(5 mL) and extracted with ethyl acetate (3ϫ10 mL). The combined Ar), 5.89 (s, 1 H, CHAr), 5.34 (d, J = 12.8 Hz, 1 H, OCH2Ar),
organic extracts were washed with brine (15 mL), dried with
Na2SO4 and concentrated in vacuo. The residue was purified by
column chromatography on silica gel (EtOAc/hexanes) to afford
the corresponding product.
4.42 (d, J = 12.8 Hz, 1 H, OCH2Ar), 3.91 (s, 3 H, OMe), 3.79 (s,
3 H, OMe) ppm. 13C NMR (75 MHz, CDCl3): δ = 159.4, 157.6,
157.4, 138.2, 138.1, 137.4, 134.1, 129.1, 128.9, 128.4, 127.5, 126.6,
125.0, 124.8, 122.1, 121.1, 120.3, 119.2, 110.5, 105.6, 99.9, 98.5,
135.2, 132.1, 70.0, 55.3, 44.3, 29.7 ppm. HRMS (EI): calcd. for
C30H26NO3 [M + H]+ 448.1907; found 448.1916.
3-(8,10-Dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-1-methyl-
1H-indole (3ba): Pale-yellow solid; m.p. 165–166 °C. IR (KBr): ν
˜
max
= 3453, 2940, 1605, 1481, 1372, 1104, 933, 750 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 6.96 (dd, J = 1.5, 7.5 Hz, 1 H, Ar), 6.90–
6.72 (m, 4 H, Ar), 6.62–6.49 (m, 3 H, Ar), 6.21 (d, J = 2.0 Hz, 1
H, Ar), 6.11 (d, J = 1.1 Hz, 1 H, Ar), 5.99 (d, J = 2.0 Hz, 1 H,
Ar), 5.63 (s, 1 H, CHAr), 5.44 (d, J = 12.6 Hz, 1 H, OCH2Ar),
4.15 (d, J = 12.8 Hz, 1 H, OCH2Ar), 3.64 (s, 3 H, OMe), 3.46 (s,
3 H, OMe), 3.34 (s, 3 H, NMe) ppm. 13C NMR (75 MHz, CDCl3):
δ = 159.2, 157.3, 157.1, 137.8, 137.3, 132.9, 128.5, 128.2, 127.3,
126.0, 123.1, 121.2, 120.9, 120.1, 120.0, 119.8, 118.6, 108.9, 105.4,
98.5, 69.7, 55.8, 55.2, 37.9, 32.5 ppm. HRMS (EI): calcd. for
C25H23NNaO3 [M + Na]+ 408.1570; found 408.1551.
3-(8,10-Dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)pentane-
2,4-dione (3bf): White solid; m.p. 121–122 °C. IR (KBr): ν
=
˜
max
3440, 3100, 2844, 1727, 1604, 1458, 1360, 1199, 939, 781 cm–1. H
NMR (300 MHz, CDCl3): δ = 7.22 (dd, J = 1.5, 7.4 Hz, 1 H, Ar),
7.16–7.13 (m, 1 H, Ar), 6.96 (d, J = 8.8 Hz, 2 H, Ar), 6.23 (d, J =
2.2 Hz, 1 H, Ar), 6.06 (d, J = 2.2 Hz, 1 H, Ar), 5.53 (d, J = 15.3 Hz,
1 H, OCH2Ar), 5.23 (d, J = 10.9 Hz, 1 H, OCH2Ar), 4.90 (s, 1 H,
CHAr), 3.80 (s, 3 H, OMe), 3.76 (d, J = 1.5 Hz, 1 H, CHCO), 3.72
(s, 3 H, OMe), 1.98 (s, 3 H, COCH3), 1.93 (s, 3 H, COCH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 203.9, 203.3, 159.5, 157.5, 156.9,
138.4, 134.2, 131.0, 128.9, 124.1, 121.2, 117.6, 102.1, 97.0, 73.1,
73.0, 55.5, 55.1, 39.9, 31.3, 29.1 ppm. HRMS (EI): calcd. for
C21H22NaO5 [M + Na]+ 377.1359; found 377.1365.
1
8,10-Dimethoxy-11-(2,4,6-trimethoxyphenyl)-6,11-dihydrodibenzo-
[b,e]oxepine (3bb): White solid; m.p. 204–205 °C. IR (KBr): ν
=
˜
max
3462, 2934, 2842, 1725, 1601, 1149, 948, 635 cm–1 1H NMR
.
2-(8,10-Dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-3-hy-
droxycyclohex-2-enone (3bg): Pale-yellow solid; m.p. 183–184 °C.
(300 MHz, CDCl3): δ = 7.05 (dd, J = 1.7, 8.4 Hz, 1 H, Ar), 6.94–
6.87 (m, 1 H, Ar), 6.7 (d, J = 8.4 Hz, 2 H, Ar), 6.23 (d, J = 18 Hz,
2 H, Ar), 6.03 (s, 2 H, Ar), 5.95 (s, 2 H, Ar), 5.63 (d, J = 13 Hz, 1
H, OCH2Ar), 4.73 (d, J = 13.5 Hz, 1 H, OCH2Ar), 3.69 (s, 3 H,
OMe), 3.67 (s, 3 H, OMe), 3.61 (s, 3 H, OMe), 3.57 (s, 6 H,
OMe) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.2, 158.8, 158.5,
158.1, 140.0, 132.4, 131.6, 128.4, 126.5, 121.9, 120.0, 116.2, 103.7,
101.7, 97.9, 91.5, 74.4, 55.1, 55.0, 55.85, 55.6, 36.8 ppm. HRMS
(EI): calcd. for C25H27O6 [M + H]+ 423.1802; found 423.1792.
IR (KBr): ν
= 3136, 2936, 2838, 1645, 1456, 1322, 1016,
˜
max
778 cm–1. 1H NMR (300 MHz, CDCl3): δ = 9.54 (s, 1 H, OH), 7.59
(d, J = 7.5 Hz, 1 H, Ar), 7.24–7.03 (m, 3 H, Ar), 6.32 (s, 1 H, Ar),
6.16 (d, J = 1.5 Hz, 1 H, Ar), 6.01 (s, 1 H, CHAr), 5.31 (d, J =
15.1 Hz, 1 H, OCH2Ar), 5.06 (d, J = 15.1 Hz, 1 H, OCH2Ar), 3.75
(s, 6 H, OMe), 2.45–2.15 [m, 4 H, (COCH2)2], 1.88–1.69 [m, 2 H,
CH2(CH2)2] ppm. 13C NMR (75 MHz, CDCl3): δ = 196.4, 170.9,
159.4, 158.8, 157.6, 134.8, 132.1, 128.2, 126.1, 120.7, 120.1, 118.5,
101.2, 98.2, 76.7, 55.5, 55.2, 36.7, 35.4, 30.0, 20.5 ppm. HRMS
(EI): calcd. for C22H23O5 [M + H]+ 367.1540; found 367.1531.
4-(8,10-Dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)phenol
(3bc): Pale-yellow oil. IR (KBr): ν
= 3428, 3011, 2943, 1604,
˜
max
1506, 1363, 1103, 938, 680 cm–1. 1H NMR (300 MHz, CDCl3): δ =
7.20–7.08 (m, 2 H, Ar), 6.91–6.75 (m, 4 H, Ar), 6.64–6.56 (m, 2 H,
Ar), 6.46 (d, J = 2.3 Hz, 1 H, Ar), 6.34 (d, J = 2.3 Hz, 1 H, Ar),
5.70 (s, 1 H, CHAr), 5.22 (d, J = 12.8 Hz, 1 H, OCH2Ar), 4.59 (s,
1 H, OH), 4.46 (d, J = 13.59 Hz, 1 H, OCH2Ar), 3.88 (s, 3 H,
OMe), 3.79 (s, 3 H, OMe) ppm. 13C NMR (75 MHz, CDCl3): δ =
159.4, 157.6, 157.3, 153.5, 138.3, 137.3, 133.7, 128.5, 128.3, 126.9,
123.9, 121.3, 120.4, 114.9, 105.4, 98.5, 70.2, 55.9, 55.3, 43.6 ppm.
HRMS (EI): calcd. for C22H21O4 [M + H]+ 349.1434; found
349.1437.
3-(8,10-Dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-hy-
droxy-2H-chromen-2-one (3bh): White solid; m.p. 194–195 °C. IR
(KBr): ν
= 3073, 2946, 1705, 1491, 1326, 1107, 940, 754 cm–1.
˜
max
1H NMR (300 MHz, CDCl3): δ = 10.19 (s, 1 H, OH), 7.74 (dd, J
= 2.2, 7.5 Hz, 1 H, Ar), 7.69 (dd, J = 1.5, 7.5 Hz, 1 H, Ar), 7.40–
7.34 (m, 1 H, Ar), 7.26–7.06 (m, 5 H, Ar), 6.34 (d, J = 3.0 Hz, 1
H, Ar), 6.28 (s, 1 H, CHAr), 6.11 (d, J = 2.3 Hz, 1 H, OCH2Ar),
5.43 (d, J = 14.4 Hz, 1 H, OCH2Ar), 5.17 (d, J = 14.4 Hz, 3 H,
Ar), 3.79 (s, 3 H, OMe), 3.76 (s, 3 H, OMe) ppm. 13C NMR
(75 MHz, CDCl3): δ = 163.6, 159.7, 159.3, 157.6, 152.1, 137.2,
133.8, 131.9, 131.5, 131.2, 129.0, 126.6, 123.5, 123.4, 121.0, 117.1,
116.9, 116.0, 109.7, 101.6, 98.2, 76.9, 55.8, 55.3, 38.4 ppm. HRMS
(EI): calcd. for C25H21O6 [M + H]+ 417.1333; found 417.1317.
3-(8,10-Dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-1H-indole
(3bd): Pale-yellow oil. IR (KBr): ν
= 3419, 3009, 2929, 2840,
˜
max
2100, 1608, 1426, 1051, 934, 750 cm–1 1H NMR (300 MHz,
.
CDCl3): δ = 7.80 (br. s, 1 H, NH), 7.35 (d, J = 7.5 Hz, 1 H, Ar),
7.30 (dd, J = 1.5, 7.5 Hz, 1 H, Ar), 7.21–7.12 (m, 2 H, Ar), 6.97
(t, J = 6.7 Hz, 1 H, Ar), 6.84 (q, J = 7.5 Hz, 4 H, Ar), 6.49 (d, J
= 2.3 Hz, 1 H, Ar), 6.47 (s, 1 H, Ar), 6.26 (d, J = 2.2 Hz, 1 H, Ar),
5.91 (s, 1 H, CHAr), 5.68 (d, J = 12.8 Hz, 1 H, OCH2Ar), 4.41 (d,
J = 12.8 Hz, 1 H, OCH2Ar), 3.93 (s, 3 H, OMe), 3.74 (s, 3 H,
OMe) ppm. 13C NMR (75 MHz, CDCl3): δ = 157.4, 157.3, 137.9,
136.8, 133.0, 128.3, 127.3, 124.0, 121.8, 121.7, 121.1, 120.2, 119.8,
119.3, 111.0, 105.6, 98.7, 69.2, 55.9, 55.3, 38.0 ppm. HRMS (EI):
calcd. for C24H22NO3 [M + H]+ 372.1594; found 372.1575.
11-Allyl-8,10-dimethoxy-6,11-dihydrodibenzo[b,e]oxepine (3bi): Yel-
low oil. IR (KBr): ν
= 3452, 2945, 2838, 1726, 1605, 1162, 952,
˜
max
1
678 cm–1. H NMR (300 MHz, CDCl3): δ = 7.10 (d, J = 7.5 Hz, 2
H, Ar), 6.93 (s, 1 H, Ar), 6.91 (s, 1 H, Ar), 6.31 (d, J = 2.2 Hz, 1
H, Ar), 6.12 (d, J = 2.2 Hz, 1 H, Ar), 5.69–5.53 (m, 1 H, CH=CH2),
5.39 (d, J = 15.0 Hz, 1 H, OCH2Ar), 4.86 (d, J = 15.0 Hz, 1 H,
OCH2Ar), 4.83–4.76 (m, 2 H, CH2=CH), 4.41 (t, J = 7.5 Hz, 1 H,
CH), 3.84 (s, 3 H, OMe), 3.70 (s, 3 H, OMe), 2.86–2.73 [m, 1 H,
CH2(CH=CH2)], 2.66–2.53 [m, 1 H, CH2(CH=CH2)] ppm. 13C
NMR (75 MHz, CDCl3): δ = 158.4, 157.44, 138.2, 137.3, 133.7,
131.8, 127.9, 123.0, 120.7, 115.4, 104.8, 102.7, 97.6, 73.1, 55.7, 55.2,
43.2, 41.5, 38.8 ppm. HRMS (EI): calcd. for C19H21O3 [M + H]+
297.1485; found 297.1471.
3-(8,10-Dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-2-phenyl-
1H-indole (3be): Pale-yellow solid; m.p. 174–175 °C. IR (KBr): ν
˜
max
1H
= 3411, 2925, 2844, 1602, 1321, 1146, 1009, 833, 690 cm–1
.
2138
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2133–2141

Dibenzo[b,e]oxepines by Tandem Reaction
3-(2-Bromo-8,10-dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-
1-methyl-1H-indole (3ca): Yellow solid; m.p. 121–124 °C. IR (KBr):
General Procedure for the Preparation of 11-Substituted Dibenzo-
[b,e]oxepines 6ba–bj: The appropriate aromatic aldehyde (1 mmol)
was added to a solution of O-benzyloxyphenol 4b (1 mmol) in
CH2Cl2 (5 mL) followed by BF3·Et2O (10 mol-%). The resulting
mixture was stirred at room temp. for a given time (Table 4). After
completion of the reaction, the mixture was quenched with water
(5 mL) and extracted with dichloromethane (3ϫ10 mL). The com-
bined organic extracts were washed with brine (15 mL), dried with
Na2SO4 and concentrated in vacuo. The residue was purified by
column chromatography on silica gel (EtOAc/hexanes) to afford
the corresponding product.
ν
= 3436, 2926, 1608, 1479, 1205, 1012, 719 cm–1. 1H NMR
˜
max
(300 MHz, CDCl3): δ = 7.40 (d, J = 2.7 Hz, 1 H, Ar), 7.25–7.16
(m, 2 H, Ar), 7.12–7.07 (m, 2 H, Ar), 6.89 (t, J = 7.3 Hz, 1 H, Ar),
6.74 (d, J = 8.2 Hz, 1 H, Ar), 6.55 (d, J = 1.8 Hz, 1 H, Ar), 6.45
(s, 1 H, Ar), 6.30 (d, J = 2.7 Hz, 1 H, Ar), 5.90 (s, 1 H, CHAr),
5.73 (d, J = 12.8 Hz, 1 H, OCH2Ar), 4.45 (d, J = 12.8 Hz, 1 H,
OCH2Ar), 3.97 (s, 3 H, OMe), 3.78 (s, 3 H, OMe), 3.69 (s, 3 H,
NCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 159.5, 157.1, 156.5,
137.4, 135.1, 131.0, 129.2, 128.5, 125.9, 122.5, 122.0, 121.4, 119.8,
119.4, 118.8, 112.7, 109.0, 105.7, 98.7, 69.8, 55.8, 55.3, 37.6,
32.6 ppm. MS (ESI): m/z = 487 [M + Na]+.
1,3,8,10-Tetramethoxy-11-phenyl-6,11-dihydrodibenzo[b,e]oxepine
(6ba): White solid; m.p. 176–178 °C. IR (KBr): ν
= 2928, 2846,
˜
max
2-Bromo-8,10-dimethoxy-11-(2,4,6-trimethoxyphenyl)-6,11-dihydro-
1736, 1610, 1461, 1154, 1108, 736, 833 cm–1. 1H NMR (CDCl3,
dibenzo[b,e]oxepine (3cb): White solid; m.p. 197–199 °C. IR (KBr):
ν
˜
300 MHz): δ = 7.12 (t, J = 7.2 Hz, 2 H, Ar), 7.05 (d, J = 7.2 Hz,
max = 3475, 2937, 2854, 1732, 1612, 1155, 965, 637 cm–1. 1H NMR 1 H, Ar), 6.90 (d, J = 7.9 Hz, 2 H, Ar), 6.47 (d, J = 2.2 MHz, 1
(300 MHz, CDCl3): δ = 7.25 (s, 1 H, Ar), 7.07 (dd, J = 1.5, 8.4 Hz,
1 H, Ar), 6.70 (d, J = 8.5 Hz, 1 H, Ar), 6.26 (s, 1 H, Ar), 6.20 (s,
H, Ar), 6.33 (s, 1 H, CHAr), 6.32 (d, J = 2.2 Hz, 1 H, Ar), 6.10
(d, J = 2.6 Hz, 1 H, Ar), 5.98 (d, J = 2.4 Hz, 1 H, Ar), 5.14 (d, J
1 H, Ar), 6.02 (s, 3 H, CHAr), 5.63 (d, J = 13.1 Hz, 1 H, OCH2Ar), = 12.6 Hz, 1 H, OCH2Ar), 4.40 (d, J = 12.6 Hz, 1 H, OCH2Ar),
4.75 (d, J = 13.1 Hz, 1 H, OCH2Ar), 3.75 (s, 3 H, OMe), 3.73 (s,
3.89 (s, 3 H, OMe), 3.79 (s, 6 H, OMe), 3.74 (s, 3 H, OMe) ppm.
3 H, OMe), 3.69 (s, 3 H, OMe), 3.62 (s, 6 H, OMe) ppm. 13C NMR 13C NMR (CDCl3, 75 MHz): δ = 159.6, 159.4, 158.8, 157.9, 146.1,
(75 MHz, CDCl3): δ = 159.6, 158.8, 158.4, 158.4, 157.7, 139.4, 137.8, 127.8, 127.0, 125.2, 124.5, 108.7, 105.2, 99.9, 98.5, 96.3, 93.7,
134.6, 134.2, 129.5, 121.8, 121.4, 115.3, 114.3, 103.8, 98.0, 91.6,
55.9, 55.7, 55.2, 55.1, 36.7, 29.7 ppm. HRMS (EI): calcd. for
C23H27BrNaO6 [M + Na]+ 503.0866; found 503.0897.
93.2, 92.5, 70.1, 56.0, 55.9, 55.3, 55.1, 33.9 ppm. HRMS (EI): calcd.
for C24H24O5 [M + H]+ 393.1697; found 393.1708.
1,3,8,10-Tetramethoxy-11-(naphthalen-1-yl)-6,11-dihydrodibenzo-
4-(2-Bromo-8,10-dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)- [b,e]oxepine (6bb): Pale-yellow solid; m.p. 204–207 °C. IR (KBr):
phenol (3cc): Pale-yellow liquid. IR (KBr): νmax = 3520, 3014, 2950,
ν
max = 2926, 2850, 1733, 1606, 1457, 1143, 1104, 783, 828 cm–1. 1H
˜
˜
1607, 1510, 1367, 1109, 944, 685 cm–1 1H NMR (300 MHz, NMR (CDCl3, 300 MHz): δ = 8.37 (t, J = 5.3 Hz, 1 H, Ar), 7.73
.
CDCl3): δ = 7.33 (d, J = 1.8 Hz, 1 H, Ar), 7.25–7.21 (m, 1 H, Ar),
6.78 (d, J = 8.2 Hz, 1 H, Ar), 6.73 (d, J = 9.2 Hz, 1 H, Ar), 6.62
(d, J = 8.3 Hz, 2 H, Ar), 6.49 (d, J = 1.8 Hz, 1 H, Ar), 6.33 (d, J
= 1.8 Hz, 1 H, Ar), 5.68 (s, 1 H, CHAr), 5.35 (s, 1 H, OH), 5.21
(t, J = 5.3 Hz, 1 H, Ar), 7.61 (d, J = 8.3 Hz, 1 H, Ar), 7.37–7.27
(m, 4 H, Ar), 6.87 (s, 1 H, CHAr), 6.44 (d, J = 2.2 Hz, 1 H, Ar),
6.19 (d, J = 3.0 Hz, 1 H, Ar), 6.12 (d, J = 3.0 Hz, 1 H, Ar), 6.05
(d, J = 2.2 Hz, 1 H, Ar), 5.60 (d, J = 13.5 Hz, 1 H, OCH2Ar), 4.51
(d, J = 12.9 Hz, 1 H, OCH2Ar), 4.46 (d, J = 12.9 Hz, 1 H, (d, J = 13.5 Hz, 1 H, OCH2Ar), 3.92 (s, 3 H, OMe), 3.81 (s, 3 H,
OCH2Ar), 3.89 (s, 3 H, OMe), 3.80 (s, 3 H, OMe) ppm. 13C NMR OMe), 3.74 (s, 3 H, OMe), 3.72 (s, 3 H, OMe) ppm. 13C NMR
(75 MHz, CDCl3): δ = 159.6, 157.6, 156.4, 153.7, 136.9, 135.7, (CDCl3, 75 MHz): δ = 159.8, 159.2, 159.1, 157.9, 157.2, 141.5,
131.4, 128.8, 128.3, 123.3, 122.3, 115.0, 113.2, 105.6, 98.62, 70.2,
50.0, 55.4, 43.3 ppm. HRMS (EI): calcd. for C20H21BrNaO4 [M +
Na]+ 427.0515; found 427.0496.
138.2, 134.0, 131.8, 128.4, 127.3, 126.8, 125.2, 125.0, 124.9, 124.8,
123.3, 112.4, 104.3, 98.7, 97.2, 93.5, 70.7, 56.2, 56.1, 55.6, 55.1,
32.6 ppm. HRMS (EI): calcd. for C28H26O5 [M + H]+ 443.1853;
found 443.1838.
3-(2-Bromo-8,10-dimethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-
1H-indole (3cd): Pale-yellow solid; m.p. 201–202 °C. IR (KBr): ν
4-(1,3,8,10-Tetramethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)phe-
˜
max
= 3420, 3100, 2940, 2842, 2110, 1610, 1488, 1321, 1051, 754 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.86 (br. s, 1 H, NH), 7.38 (s, 1
H, Ar), 7.19 (d, J = 9.2 Hz, 1 H, Ar), 7.14 (d, J = 7.3 Hz, 1 H,
nol (6bc): White solid; m.p. 218–221 °C. IR (KBr): ν
= 3397,
˜
max
1
2936, 2843 (s), 2359, 1734, 1610, 1206, 1099, 833 cm–1. H NMR
(CDCl3, 300 MHz): δ = 6.76 (d, J = 8.4 Hz, 2 H, Ar), 6.58 (d, J =
Ar), 7.10–6.98 (m, 2 H, Ar), 6.86 (t, J = 7.3 Hz, 1 H, Ar), 6.70 (d, 8.4 Hz, 2 H, Ar), 6.46 (d, J = 2.2 Hz, 1 H, Ar), 6.32 (d, J = 2.2 Hz,
J = 9.2 Hz, 1 H, Ar), 6.50 (d, J = 12.9 Hz, 1 H, Ar), 6.25 (s, 1 H, 2 H, Ar), 6.23 (s, 1 H, CHAr), 6.09 (d, J = 2.5 Hz, 1 H, Ar), 5.98
Ar), 5.87 (s, 1 H, CHAr), 5.65 (d, J = 12.9 Hz, 1 H, OCH2Ar),
4.39 (d, J = 11.9 Hz, 1 H, OCH2Ar), 3.95 (s, 3 H, OMe), 3.74 (s,
3 H, OCH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 157.4, 157.3,
137.9, 136.8, 133.0, 128.3, 127.3, 124.0, 121.8, 121.7, 121.2, 120.2,
119.8, 119.3, 111.0, 105.6, 98.8, 69.8, 55.9, 55.3, 39.0 ppm. HRMS
(EI): calcd. for C24H21BrNO3 [M + H]+ 450.0699; found 450.0697.
(d, J = 2.2 Hz, 1 H, Ar), 5.17 (d, J = 12.6 Hz, 1 H, OCH2Ar), 4.41
(d, J = 12.6 Hz, 1 H, OCH2Ar), 3.88 (s, 3 H, OMe), 3.79 (s, 6 H,
OMe), 3.74 (s, 3 H, OMe) ppm. 13C NMR (CDCl3, 75 MHz): δ =
159.5, 159.3, 159.2, 158.8, 157.8, 153.3, 138.2, 137.8, 128.1, 124.5,
114.7, 109.0, 105.2, 98.5, 96.3, 92.5, 70.1, 56.1, 55.9, 55.3, 55.1,
33.2 ppm. HRMS (EI): calcd. for C24H24O6 [M + H]+ 409.1646;
found 409.1656.
8,10-Dimethoxy-11-(2,4,6-trimethoxyphenyl)dibenzo[b,e]oxepin-
6(11H)-one (3db): White solid; m.p. 147–148 °C. IR (KBr): ν
=
11-(3,5-Dimethoxyphenyl)-1,3,8,10-tetramethoxy-6,11-dihydrodi-
˜
max
3461, 2936, 2840, 1727, 1365, 1203, 1053, 827, 755 cm–1. H NMR
(300 MHz, CDCl3): δ = 7.68 (d, J = 15 Hz, 1 H, Ar), 7.45 (d, J =
7.5 Hz, 1 H, Ar), 7.17–6.95 (m, 4 H, Ar), 6.52 (d, J = 2.2 Hz, 1 H,
benzo[b,e]oxepine (6bd): White solid; m.p. 159–162 °C. IR (KBr):
1
ν
˜
max = 2998, 2959, 2931, 2839, 1605, 1458, 1151, 710, 833 cm–1. 1H
NMR (CDCl3, 300 MHz): δ = 6.46 (s, 1 H, Ar), 6.33 (d, J = 2.1 Hz,
Ar), 6.19 (s, 1 H, CHAr), 6.0 (s, 2 H, OCH2Ar), 3.81 (s, 6 H, OMe), 1 H, Ar), 6.25 (s, 1 H, CHAr), 6.14 (s, 1 H, Ar), 6.09 (d, J = 2.2 Hz,
3.72 (s, 3 H, OMe), 3.63 (s, 6 H, OMe) ppm. 13C NMR (75 MHz,
CDCl3): δ = 158.8, 158.4, 157.0, 157.7, 139.6, 132.0, 131.2, 127.9,
126.0, 121.5, 119.6, 115.8, 103.3, 97.5, 91.1, 55.4, 55.2, 54.7, 54.6,
36.3 ppm. HRMS (EI): calcd. for C25H25O7 [M + H]+ 437.1595;
found 437.1611.
1 H, Ar), 6.05 (s, 2 H, Ar), 5.97 (d, J = 2.2 Hz, 1 H, Ar), 5.23 (d,
J = 13.2 Hz, 1 H, OCH2Ar), 4.42 (d, J = 13.2 Hz, 1 H, OCH2Ar),
3.88 (s, 3 H, OMe), 3.79 (s, 6 H, OMe), 3.73 (s, 3 H, OMe), 3.64
(s, 6 H, OMe) ppm. 13C NMR (CDCl3, 75 MHz): δ = 160.4, 159.7,
159.4, 158.7, 157.8, 149.0, 137.8, 124.2, 108.4, 106.0, 105.3, 98.6,
Eur. J. Org. Chem. 2011, 2133–2141
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2139

C. R. Reddy, P. Ramesh, N. N. Rao, S. A. Ali
FULL PAPER
96.5, 96.3, 92.5, 70.1, 56.1, 56.0, 55.3, 55.0 ppm. HRMS (EI): calcd.
for C26H28O7 [M + H]+ 453.1908; found 453.1893.
759 cm–1. 1H NMR (CDCl3, 300 MHz): δ = 7.55–7.50 (m, 2 H,
Ar), 7.34–7.26 (m, 3 H, Ar), 7.30 (s, 1 H, Ar), 7.15–7.05 (m, 1 H,
Ar), 6.40 (d, J = 3.0 Hz, 1 H, Ar), 6.28 (d, J = 3.0 Hz, 1 H, Ar),
6.13 (s, 1 H, CHAr), 6.10 (d, J = 2.3 Hz, 1 H, Ar), 6.02 (d, J =
2.3 Hz, 1 H, Ar), 5.56 (d, J = 12.8 Hz, 1 H, OCH2Ar), 4.59 (d, J
= 12.8 Hz, 1 H, OCH2Ar), 3.89 (s, 3 H, OMe), 3.82 (s, 3 H, OMe),
3.78 (s, 3 H, OMe), 3.74 (s, 3 H, OMe),1.96 (s, 3 H, ArCH3) ppm.
13C NMR (CDCl3, 75 MHz): δ = 159.6, 159.2, 159.1, 158.5, 157.6,
148.0, 140.1, 138.1, 129.0, 127.0, 126.8, 125.2, 122.1, 118.2, 111.0,
104.3, 98.1, 96.8, 93.0, 70.8, 56.0, 55.7, 55.2, 55.1, 25.9, 12.1 ppm.
HRMS (EI): calcd. for C28H28N2O5 [M + H]+ 473.2071; found
473.2081.
1,3,8,10-Tetramethoxy-11-(4-nitrophenyl)-6,11-dihydrodibenzo[b,e]-
oxepine (6be): Viscous liquid. IR (KBr): ν
= 2938, 2842, 1727,
˜
max
1609, 1345, 1269, 1148, 1106, 735, 832 cm–1. 1H NMR (CDCl3,
300 MHz): δ = 8.02 (d, J = 9.0 Hz, 2 H, Ar), 7.12 (d, J = 9.0 Hz,
2 H, Ar), 6.48 (d, J = 2.2 Hz, 1 H, Ar), 6.35 (s, 1 H, CHAr), 6.30
(d, J = 2.2 Hz, 1 H, Ar), 6.14 (d, J = 2.2 Hz, 1 H, Ar), 6.03 (d, J
= 2.2 Hz, 1 H, Ar), 5.02 (d, J = 12.8 Hz, 1 H, OCH2Ar), 4.51 (d,
J = 12.8 Hz, 1 H, OCH2Ar), 3.90 (s, 3 H, OMe), 3.81 (s, 6 H,
OMe), 3.75 (s, 3 H, OMe) ppm. 13C NMR (CDCl3, 75 MHz): δ =
160.1, 159.7, 159.0, 158.9, 157.8, 154.2, 145.7, 137.8, 127.9, 123.1,
122.2, 108.8, 104.7, 98.4, 96.7, 93.0, 70.7, 56.04, 56.00, 55.3, 55.2,
34.5 ppm. HRMS (EI): calcd. for C24H23NO7 [M + H]+ 438.1547;
found 438.1557.
(E)-1,3,8,10-Tetramethoxy-11-styryl-6,11-dihydrodibenzo[b,e]-
oxepine (6bj): Viscous liquid. IR (KBr): ν
= 2931, 2844, 1611,
˜
max
1147, 1107, 768, 821 cm–1. H NMR (CDCl3, 300 MHz): δ = 7.23
(d, J = 6.8 Hz, 2 H, Ar), 7.16 (t, J = 7.5 Hz, 2 H, Ar), 7.06 (t, J =
6.8 Hz, 1 H, Ar), 6.45 (dd, J = 4.5, 15.8 Hz, 2 H, Ar), 6.33 (d, J =
6.8 Hz, 1 H, Ar), 6.10 (br. s, 1 H, Ar), 5.99 (br. s, 2 H, CH), 5.79
(br. s, 1 H, CHAr), 5.57 (d, J = 12.8 Hz, 1 H, OCH2Ar), 4.59 (d,
J = 12.8 Hz, 1 H, OCH2Ar), 3.86 (s, 3 H, OMe), 3.85 (s, 3 H,
OMe), 3.80 (s, 3 H, OMe), 3.73 (s, 3 H, OMe) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 159.3, 159.3, 159.1, 157.6, 138.5, 134.8,
137.6, 126.1, 126.6, 127.7, 128.2, 127.0, 127.8, 108.7, 104.8, 98.6,
96.2, 92.7, 70.9, 56.0, 55.9, 55.3, 55.2, 33.2 ppm. HRMS (EI): calcd.
for C26H26O5 [M + H]+ 419.1853; found 419.1862.
1
1,3,8,10-Tetramethoxy-11-(thiophen-2-yl)-6,11-dihydrodibenzo[b,e]-
oxepine (6bf): Pale-yellow solid; m.p. 185–188 °C. IR (KBr): ν
=
˜
max
2929, 2843, 1734, 1608, 1148, 1108, 1056, 814, 700 cm–1. H NMR
(CDCl3, 300 MHz): δ = 6.97 (d, J = 5.3 Hz, 1 H, Ar), 6.78–6.76
(m, 1 H, Ar), 6.45 (d, J = 2.3 Hz, 1 H, Ar), 6.41 (s, 1 H, CHAr),
6.39 (t, J = 1.5 Hz, 1 H, Ar), 6.36 (d, J = 2.3 Hz, 1 H, Ar), 6.10
(d, J = 2.3 Hz, 1 H, Ar), 5.97 (d, J = 3.0 Hz, 1 H, Ar), 5.36 (d, J
= 12.8 Hz, 1 H, OCH2Ar), 4.50 (d, J = 12.8 Hz, 1 H, OCH2Ar),
3.89 (s, 3 H, OMe), 3.84 (s, 3 H, OMe), 3.81 (s, 3 H, OMe), 3.74
(s, 3 H, OMe) ppm. 13C NMR (CDCl3, 75 MHz): δ = 159.8, 159.7,
159.2, 158.9, 157.5, 151.8, 138.5, 126.3, 123.5, 123.1, 123.6, 109.8,
105.3, 98.5, 96.4, 92.7, 70.6, 56.1, 55.3, 55.2, 31.2 ppm. HRMS
(EI): calcd. for C22H22O5S [M + H]+ 399.1261; found 399.1267.
1
1-[2-(3,5-Dimethoxybenzyloxy)phenyl]but-3-en-1-ol (8): Pale-yellow
liquid. IR (KBr): ν
= 3448, 3070, 2934, 2842, 1720, 1603, 1487,
˜
max
1367, 1287 cm–1. H NMR (300 MHz, CDCl3): δ = 7.55 (dd, J =
7.3, 1.1 Hz, 1 H, Ar), 7.16 (dt, J = 8.1, 1.5 Hz, 1 H, Ar), 6.93 (t, J
= 7.3 Hz, 1 H, Ar), 6.85 (d, J = 8.1 Hz, 1 H, Ar), 6.50 (d, J =
2.0 Hz, 1 H, Ar), 6.34 (t, J = 2.0 Hz, 1 H, Ar), 5.89–5.74 (m, 1 H,
CH=CH2), 5.14–4.96 (m, 5 H, OCH2Ar, CH2=CH, ArCHOH),
3.77 (s, 6 H, 2 OMe) ppm. 13C NMR (75 MHz, CDCl3): δ = 158.7,
158.3, 157.8, 138.2, 137.2, 133.7, 131.8, 127.9, 122.9, 121.8, 120.7,
115.3, 102.8, 97.6, 73.1, 55.7, 55.2, 43.2, 41.5 ppm. MS (ESI): m/z
= 315 [M + H]+.
1
3-(1,3,8,10-Tetramethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-
1-tosyl-1H-indole (6bg): White solid; m.p. 204–207 °C. IR (KBr):
ν
˜
max = 2928, 2853, 1731, 1609, 1173, 1144, 1109, 810, 740 cm–1. 1H
NMR (CDCl3, 300 MHz): δ = 7.89 (d, J = 7.7 Hz, 1 H, Ar), 7.63
(d, J = 8.7 Hz, 2 H, Ar), 7.17 (m, 3 H, Ar), 7.10 (d, J = 7.7 Hz, 1
H, Ar), 7.01 (t, J = 7.7 Hz, 1 H, Ar), 6.96 (s, 1 H, Ar), 6.48 (d, J
= 1.9 Hz, 1 H, Ar), 6.35 (s, 1 H, CHAr), 6.26 (d, J = 1.9 Hz, 1 H,
Ar), 6.14 (d, J = 1.9 Hz, 1 H, Ar), 6.05 (d, J = 1.9 Hz, 1 H, Ar),
5.49 (d, J = 12.6 Hz, 1 H, OCH2Ar), 4.43 (d, J = 12.6 Hz, 1 H,
OCH2Ar), 3.93 (s, 3 H, OMe), 3.80 (s, 3 H, OMe), 3.78 (s, 6 H,
OMe), 2.35 (s, 3 H, CH3) ppm. 13C NMR (CDCl3, 75 MHz): δ =
159.7, 159.4, 159.0, 158.5, 157.3, 144.4, 138.4, 135.9, 135.0, 129.9,
129.5, 128.6, 126.6, 125.0, 124.1, 123.0, 121.4, 120.5, 113.6, 108.8,
104.9, 98.6, 96.7, 92.8, 69.8, 55.9, 55.2, 55.1, 27.4, 21.4 ppm.
HRMS (EI): calcd. for C33H31NO7S [M + H]+ 586.1894; found
586.1869.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, spectroscopic data for 1b–d, 3a, 4a
and 4b and 1H and 13C NMR spectra for all the reaction products.
Acknowledgments
P. R. thanks the University Grants Commission (UGC) and
N. N. R. thanks the Council of Scientific and Industrial Research
(CSIR), New Delhi for research fellowships.
3-(1,3,8,10-Tetramethoxy-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4H-
chromen-4-one (6bh): White solid; m.p. 213–216 °C. IR (KBr): ν
˜
max
= 3081, 2927, 2843, 1728, 1649, 1609, 1144, 1105, 831, 752 cm–1.
1H NMR (CDCl3, 300 MHz): δ = 8.12 (dd, J = 8.3, 1.5 Hz, 1 H,
Ar), 7.56 (d, J = 1.5 Hz, 1 H, Ar), 7.51 (dd, J = 6.7, 1.5 Hz, 1 H,
Ar), 7.28 (dd, J = 16.6, 8.3 Hz, 1 H, Ar), 6.40 (d, J = 2.3 Hz, 1 H,
Ar), 6.33 (d, J = 1.5 Hz, 1 H, Ar), 6.17 (d, J = 2.2 Hz, 1 H, Ar),
6.15 (d, J = 3.0 Hz, 1 H, CHAr), 6.04 (d, J = 2.3 Hz, 1 H, Ar),
5.51 (d, J = 14.3 Hz, 1 H, OCH2Ar), 4.74 (d, J = 14.3 Hz, 1 H,
OCH2Ar), 3.90 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 3.76 (s, 3 H,
OMe), 3.72 (s, 3 H, OMe) ppm. 13C NMR (CDCl3, 75 MHz): δ =
176.5, 159.9, 159.6, 159.2, 158.7, 158.4, 155.9, 154.4, 138.4, 132.7,
127.7, 126.0, 124.3, 124.1, 119.0, 117.6, 111.3, 103.0, 98.1, 97.2,
94.0, 71.7, 56.1, 56.0, 55.1, 27.7 ppm. HRMS (EI): calcd. for
C27H24O7 [M + H]+ 461.1595; found 461.1603.
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Received: December 29, 2010
Published Online: March 2, 2011
Eur. J. Org. Chem. 2011, 2133–2141
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2141