Palladium-catalyzed 8-exo trig intramolecular heck reaction under microwave irradiation in the presence of basic alumina

Article abstract of DOI:10.1080/00397911.2011.578327

The Heck cross-coupling reaction has been employed for efficient conversion of quinolines to benzoxocinoquinoline through a microwave-assisted palladium-catalyzed intramolecular cyclization in the presence of basic alumina.

Full text of DOI:10.1080/00397911.2011.578327

Synthetic Communications1, 42: 3166–3176, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.578327
PALLADIUM-CATALYZED 8-EXO TRIG
INTRAMOLECULAR HECK REACTION UNDER
MICROWAVE IRRADIATION IN THE PRESENCE OF
BASIC ALUMINA
Pritam Saha,1 Shyamal Mondal,1 Abhijit Hazra,1
Subhendu Naskar,1 Arindam Maity,1 Krishnendu B. Sahu,1
Rupankar Paira,1 Saktipada Das,2 Sukdeb Banerjee,1 and
Nirup B. Mondal1
1Department of Chemistry, Indian Institute of Chemical Biology, Council of
Scientific and Industrial Research, Jadavpur, Kolkata, India
2Department of Chemistry, University of Kalyani, Kalyani, India
GRAPHICAL ABSTRACT
Abstract The Heck cross-coupling reaction has been employed for efficient conversion of
quinolines to benzoxocinoquinoline through a microwave-assisted palladium-catalyzed
intramolecular cyclization in the presence of basic alumina.
Keywords Basic alumina; benzoxocinoquinoline; Heck cross-coupling reaction; micro-
wave irradiation; solid-phase synthesis
Received January 31, 2011.
Address correspondence to Nirup B. Mondal, Indian Institute of Chemical Biology, 4 Raja S C
Mullick Road, Jadavpur, Kolkata- 700 032, India. E-mail: Nirup@iicb.res.in
3166

FUSED TETRACYCLIC BENZOXOCINOQUINOLINC
3167
INTRODUCTION
Palladium-catalyzed C-C and C-heteroatom bond-forming reactions have
gained enormous interest nowadays in organic synthesis for the construction of small
to medium-sized heteroaromatics[1,2] because many natural products, drugs, and pre-
clinical leads contain medium-sized heterocycles fused to aryl rings, which are used
as antipsychotic drugs.[2c] Among several palladium-catalyzed reactions, the use of
the Heck reaction[3] in the synthesis of organic molecules through C-C bond forma-
tion is quite significant. Also, the use of methodological tools such as
microwave-assisted solid-phase organic synthesis provides powerful means for the
preparation of compound libraries[4] and is well known for achieving energy
efficiency and enhancing the rate of reaction as well as product yields.[5] Moreover,
the possibility of using a solid-supported reaction is particularly attractive. It is well
documented that organic compounds get adsorbed on the surface of inorganic oxides
such as alumina or silica, which themselves do not absorb or restrict the transmission
of microwave irradiation.[6] This is also the case with reagents immobilized on
porous solid supports, which have an advantage over the conventional
solution-phase reactions because of the good dispersion of active sites, associated
selectivities, and easier workup.[6] Our recent success in establishing a basic
alumina-supported, Suzuki[7a] and Sonogashira[7b] reaction for C-C bond formation
coupled with the biological importance of oxa-heterocycles[8] prompted us to apply
the methodology for rapid and efficient synthesis of oxa-aza heterocyclic moieties by
intramolecular Heck reaction. It is worth mentioning that several groups[9] have
reported the formation of medium-sized heterocycles by palladium-catalyzed Heck
reaction,[10] where harsh reaction conditions were used. Some groups performed
the synthesis through sequential changes in catalysts, bases, ligands, and solvents
or through a radical pathway[11] in the conventional heating process. The Heck pre-
cursor was also synthesized through Wittig olefination[12] or O-allylation and O-ben-
zylation pathways in organic solvent, and these intramolecular Heck reactions
sometimes produced eight-membered or nine- membered compound or even both.
None have used microwave as a tool and solid support in reactions for synthesizing
heterocycles either as Heck precursor or in Heck reaction. In this communication, we
describe palladium-catalyzed synthesis of exclusively eight-membered oxa-aza het-
erocycles by microwave-assisted basic alumina–supported Heck reaction without
use of any external base. To the best of our knowledge, this is the first report of ben-
zoxocinoquinoline synthesis through the application of Heck reaction.
RESULTS AND DISCUSSION
The easy availability of 8-hydroxyquinolines (1a–c) prompted us to synthesize
oxa-aza heterocycles from these starting materials employing the Heck reaction. We
planned to insert an allyl group ortho to the phenolic group exploiting the Claisen
rearrangement. Conversion of the C-allyl phenol to its 2-bromobenzylether should
be easy, furnishing the substrate for our Heck cyclization step. At the outset, we
chose 5-chloro-8-hydroxyquinoline (1a) and allyl bromide as model reaction part-
ners to produce O-allyl-quinoline (2a). The basic property of basic alumina[7]
was utilized for the synthesis of 2a under a microwave environment. The

3168
P. SAHA ET AL.
Scheme 1. Synthesis of benzoxocinoquinoline through microwave-assisted palladium-catalyzed intramol-
ecular Heck reaction. (Figure is provided in color online.)
O-allyl-quinoline (2a) was then subjected to Claisen rearrangement utilizing silica gel
as the solid support as the acidic nature of the silica surface promotes the rearrange-
ment leading toward the synthesis of C-allyl product (3a).[13] The physisorption of
reactants on the silica surface leads to an increase in local concentration, which in
turn enhances the rate of reaction. Compounds 3a was then reacted with 2-bromo
benzylbromide for the preparation of the O- benzoylated product 4a, the desired
substrate for Heck reaction, as shown in Scheme 1.
To optimize the yield of the Heck reaction products, a systematic study was
performed on our model precursor 4a, varying the catalysts, bases, solvents, solid
supports, temperature, and time period. The results of the systematic studies revealed
that the reactions catalyzed by different palladium catalysts like PdCl2 and
Pd(PPh3)2Cl2 with different bases like K2CO3, Ag2CO3, Et3N, and NaOAc in differ-
ent solvents like dimethylformamide (DMF), toluene or dioxane in the presence of
tetrabutylammonium bromide (TBAB) at 120 ꢀC (oil bath) for 4–6 h were either inef-
fective or gave poor (20%) to moderate (48%) yield of 5a. However, when the reac-
tion was carried out in DMF in the presence of Pd(OAc)2 using TBAB as moderator
and KOAc as base under microwave irradiation (120 ꢀC) for 45 min, an increase in
yield (57%) was observed. The efficacy of Pd(OAc)2 as catalyst prompted us to
extend the study to evaluate the effect of various solid supports under microwave
irradiation. The results are summarized in Table 1.
The results showed that the use of magnesium oxide, titanium dioxide, or
montmorillonite K-10 as a solid support was unsatisfactory. There was some
improvement in yield using activated carbon (50%, entry 9), silica gel (56%, entry

FUSED TETRACYCLIC BENZOXOCINOQUINOLINC
3169
Table 1. Optimization of catalyst [Pd(OAc)2] loading on different solid supportsa
Catalyst
(mol %) Temperature (ꢀC) Time (min) Yieldb (%)
Entry
Solid support
Using KOAc as base
1
MgO
MgO
10
20
10
20
10
20
10
10
10
20
10
20
10
20
10
20
10
20
120
120
120
120
120
120
90
30
30
20
20
20
20
17
17
15
15
15
15
15
15
15
15
12
12
NRc
2
NR
33
33
39
39
43
48
50
50
56
56
59
59
68
68
87
87
3
TiO2
TiO2
4
5
Montmorillonite K10
Montmorillonite K10
Activated carbon
Activated carbon
Activated carbon
Activated carbon
Silica gel
6
7
8
110
120
120
120
120
120
120
120
120
120
120
9
10
11
12
Silica gel
13
14
Acidic alumina
Acidic alumina
Neutral alumina
Neutral alumina
Basic alumina
Basic alumina
15
16
17
18
Without KOAc:
19
20
21
22
Basic alumina
Basic alumina
Basic alumina
Basic alumina
10
20
6
120
120
120
120
12
12
12
12
87
87
87
64
3
aAll the studies were performed by using 4a, Pd(OAc)2 catalyst under microwave irradiation at 250 W.
bIsolated yield.
cNo reaction.
11), acidic alumina (59%, entry 13), or neutral alumina (68%, entry 15), but
the best results were obtained using basic alumina, which gave the product in
87% yield (entry 17) even in the absence of KOAc as a base (entries 19, 20,
and 21).
The good performance of basic alumina,[6] for the synthesis of benzoxocinoqui-
noline by the Heck reaction, may be attributed to its role as a base that leads to the
regeneration of palladium(0) by base-induced proton abstraction from the H-[Pd]-Br
species (Scheme 2). The reaction proceeds in the 8-exo trig mode, which is far less
sterically demanding, whereas the endo trig mode of cyclization requires the olefinic
bond to be positioned inside the intermolecular k complex. Because of geometry, it is
improbable to have flexible tether between the olefin bond and bending of aromatic
ring in proper conformation.[14]
To rationalize the applicability of this method for the synthesis of
eight-membered oxa-heterocycles, we extended the study by varying the functional
groups in the Heck precursors (4b–e) (Table 2). Here also we observed the formation
of the eight-member exo trig ring products rather than the nine-endo trig mode of
cyclization, probably because of the less sterically demanding environment in the
eight-exo trig product.[15,16] The results are summarized in Table 2.

3170
P. SAHA ET AL.
Scheme 2. Plausible pathway for basic alumina-mediated Heck reaction.
We then investigated the reusability of basic alumina for the reaction of 4a. It
was found that the recovered basic alumina could be recycled three to four times
with insignificant change in its activity. The recycling process involves proper
washing, first with acetone and then with water, and calcination in an oven for
5 h at 150 ꢀC. To examine the advantage of using microwave irradiation, we also
performed the reaction with 4a in an oil bath at 120 ꢀC under otherwise identical
reaction conditions. It is noteworthy that only 18% yield of 5a was obtained after
15 h of reaction, whereas 87% yield was obtained in 12 min under microwave
irradiation.
EXPERIMENTAL
Representative Procedure for o-Allyl-quinoline (2a–c)
Chloroform was added to a mixture of 8-hydroxyquinoline derivatives (1a–c)
(1 equiv.) and basic alumina (500 mg) in a round-bottomed flask. The organic layer
was evaporated to dryness under reduced pressure. The solid mixture was stirred at
room temperature for an additional 10–15 min to ensure efficient mixing, followed
by subsequent addition of allyl bromide (1.1 equiv.). The flask was then fitted with
a septum, and the mixture was subjected to irradiation in a microwave reactor
(CEM, Discover, USA) at 65 ꢀC (250 W) for 8 min (as monitored by thin-layer chro-
matography, TLC). After cooling, ethyl acetate was added, and the slurry stirred at

FUSED TETRACYCLIC BENZOXOCINOQUINOLINC
3171
Table 2. Intramolecular Heck cross-coupling reaction of 8-hydroxyquinolines for the synthesis of benzox-
ocinoquinolines under microwave irradiation
Entrya
Substrate
Product
Yieldb%
1
87
2
83
3
86
4
84
5
81
aReaction conditions: basic alumina (250 mg), Heck precursor (1 equiv.), Pd(OAc)2 (6 mol%), and
TBAB, under microwave irradiation (250 W), reaction time 12 min, temperature 120 ꢀC.
bIsolated yield. The products were characterized by MS and 1H and 13C NMR spectroscopy.

3172
P. SAHA ET AL.
room temperature for 10 min. The mixture was vacuum filtered through a sintered
glass funnel, and the product was isolated via flash chromatography to yield the
desired O-allyl-quinolines (2a–c)compound.
Representative Procedure for Heck Precursor (4a–e)
Chloroform was added to a mixture of C-allyl-quinoline derivatives (3a–c)
(1 equiv.) and basic alumina (500 mg) in a round-bottomed flask. The organic layer
was evaporated to dryness under reduced pressure. The solid mixture was stirred at
room temperature for an additional 10–15 min to ensure efficient mixing, followed
by subsequent addition of 2-bromo benzylbromide (1.2 equiv.). The flask was then
fitted with a septum, and the mixture was subjected to irradiation in a microwave
reactor (CEM, Discover, USA) at 85 ꢀC (250 W) for 8 min (as monitored by
TLC). After cooling, ethyl acetate was added, and the slurry was stirred at room
temperature for 10 min. The mixture was vacuum filtered through a sintered glass
funnel and the product was isolated via flash chromatography to yield the desired
Heck precursors (4a–e).
Representative Procedure for Heck Reaction
Chloroform was added to a mixture of Heck precursors (4a–e) (1 equiv.) and
basic alumina (250 mg) in a round-bottomed flask. The organic layer was evaporated
to dryness under reduced pressure. The solid mixture was stirred at room tempera-
ture for an additional 10–15 min to ensure efficient mixing, followed by subsequent
addition of Pd(OAc)2 (6 mol%). The flask was then fitted with a septum, and the mix-
ture was subjected to irradiation in a microwave reactor (CEM, Discover, USA) at
120 ꢀC (250 W) for 12 min (as monitored by TLC). After cooling, ethyl acetate was
added, and the slurry was stirred at room temperature for 10 min. The mixture
was vacuum filtered through a sintered glass funnel, and the product was isolated
via flash chromatography to yield the benzoxocinoquinolines (5a–e). In the recycling
experiment, the residue obtained was washed with acetone and water (three or four
times) and subjected to calcination at 150 ꢀC. The calcinated material could be
further be utilized in the coupling reaction.
Data for Compound 4a
Rf(30% petroleum ether–EtOAc) 0.38. Grey solid; mp 92–94oC. 1H NMR
(600 MHz, CDCl3): d 3.54 (2H, d, J ¼ 6.6 Hz), 5.06 (2H, m), 5.49 (2H, s), 5.86
(1H, m), 7.20 (1H, t, J ¼ 7.8 Hz), 7.37 (1H, t, J ¼ 7.2 Hz), 7.47 (1H, s), 7.50 (1H,
q, J ¼ 4.2 Hz), 7.58 (1H, d, J ¼ 7.8 Hz), 7.77 (1H, d, J ¼ 7.2 Hz), 8.54 (1H, dd,
J1 ¼ 8.4 Hz, J2 ¼ 1.2 Hz), 8.98 (1H, dd, J1 ¼ 3.0 Hz, J2 ¼ 1.2 Hz) ; 13C NMR (CDCl3,
150 MHz): d 34.2 (CH2), 75.6 (CH2), 116.7 (CH2), 121.4 (CH), 122.7 (CH), 125.9 (C),
126.2 (C), 127.5 (CH), 128.5 (CH), 129.2 (CH), 129.7 (CH), 132.4 (CH), 133.1 (C),
133.2 (C), 136.0 (CH), 137.3 (C), 143.5 (C), 150.0 (CH), 151.0 (C). ESI-MS: m=z
388 [M þ H]þ, 410 [M þ Na]þ.

FUSED TETRACYCLIC BENZOXOCINOQUINOLINC
3173
Data for Compound 4b
Rf(30% petroleum ether–EtOAc) 0.40. Yellowish brown solid; mp 102–104oC.
1H NMR (600 MHz, CDCl3): d 2.61 (3H, s), 3.50 (2H, d, J ¼ 7.8 Hz), 4.98 (2H, m),
5.36 (2H, s), 5.74 (1H, m) 7.07 (1H, m), 7.14 (1H, d, J ¼ 7.2 Hz), 7.20 (1H, d,
J ¼ 6.6 Hz), 7.28 (1H, t, J ¼ 6.6 Hz), 7.37 (1H, s), 7.43 (1H, m), 7.53 (1H, d,
J ¼ 7.2 Hz), 8.41 (1H, m) ; 13C NMR (CDCl3, 150 MHz): d 22.3 (CH3), 34.2
(CH2), 75.1 (CH2), 116.1 (CH2), 121.9 (CH), 122.2 (C), 125.7 (C), 125.9 (C), 127.1
(CH), 127.5 (CH), 128.8 (CH), 129.4 (CH), 133.0 (CH), 133.1 (CH), 135.8 (CH),
137.1 (C), 138.8 (C), 142.7 (C), 150.8 (C), 155.6 (CH). ESI-MS: m=z 368 [M þ H]þ,
390 [MþNa]þ.
Data for Compound 4c
Rf(30% petroleum ether–EtOAc) 0.40. Yellowish brown solid; mp 112–114oC.
1H NMR (600 MHz, CDCl3): d 3.50 (2H, d, J ¼ 7.2 Hz), 4.93 (2H, m), 5.40 (2H, s),
5.78 (1H, m), 7.05 (1H, t, J ¼ 7.8 Hz), 7.16 (1H, d, J ¼ 7.2 Hz), 7.20 (1H, d,
J ¼ 7.2 Hz), 7.30 (1H, t, J ¼ 7.2 Hz), 7.39 (1H, s), 7.43 (1H, m), 7.52 (1H, d,
J ¼ 7.2 Hz), 8.44 (1H, dd, J1 ¼ 7.8 Hz, J2 ¼ 1.2 Hz), 8.80 (1H, dd, J1 ¼ 2.4 Hz,
J2 ¼ 1.2 Hz); 13C NMR (CDCl3, 150 MHz): d 33.9 (CH2), 76.8 (CH2), 115.8 (CH2),
116.0 (C), 118.5 (CH), 120.4 (CH), 122.0 (C), 125.7 (C), 127.0 (CH), 127.8
(CH), 128.0 (CH), 132.9 (CH), 133.0 (CH), 133.8 (CH), 135.6 (C), 139.1 (C), 142.5
(C), 148.5 (CH), 153.2 (CH). ESI-MS: m=z 354 [M þ H]þ.
Data for Compound 4d
Rf(30% petroleum ether–EtOAc) 0.45. Grey solid; mp 82–84oC. 1H NMR
(600 MHz, CDCl3): d 3.51 (2H, d, J ¼ 7.2 Hz), 3.70 (3H, s), 4.98 (2H, m), 5.42
(2H, s), 5.82 (1H, m), 7.29 (1H, t, J ¼ 6.6 Hz), 7.42 (1H, m), 7.44 (1H, d, J ¼ 7.2 Hz),
7.56 (1H, d, J ¼ 7.8 Hz), 7.72 (1H, d, J ¼ 7.2 Hz), 8.53 (1H, m), 8.90 (1H, m) ; 13C
NMR (CDCl3, 150 MHz): d 34.0 (CH2), 56.6 (CH3), 75.8 (CH2), 112.7 (CH2),
116.4 (CH), 117.2 (CH), 121.0 (CH), 121.8 (C), 125.3 (C), 126.4 (C), 128.0 (CH),
129.6 (CH), 132.2 (CH), 133.1 (C), 135.4 (CH), 137.5 (C), 137.9 (C), 150.3 (CH),
151.0 (C), 158.5 (C). ESI-MS: m=z 418 [M þ H]þ, 440 [M þ Na]þ.
Data for Compound 4e
1
Rf(30% petroleum ether–EtOAc) 0.43. Light yellow solid; mp 88–90oC. H
NMR (600 MHz, CDCl3): d 3.53 (2H, d, J ¼ 6.6 Hz), 4.95 (2H, m), 5.40 (2H, s),
5.85 (1H, m), 7.32 (1H, d, J ¼ 7.2 Hz), 7.42 (1H, d, J ¼ 6.0 Hz), 7.52 (1H, m), 7.57
(1H, d, J ¼ 7.2 Hz), 7.70 (1H, d, J ¼ 7.2 Hz), 8.49 (1H, m), 8.93 (1H, m); 13C
NMR (CDCl3, 150 MHz): d 34.0 (CH2), 74.6 (CH2), 111.5 (CH2), 116.0 (CH),
116.9 (CH), 121.0 (CH), 121.8 (C), 124.8 (C), 125.9 (C), 128.4 (CH), 129.2 (CH),
132.5 (CH), 133.1 (C), 135.2 (CH), 136.9 (C), 137.3 (C), 150.1 (CH), 151.6 (C),
155.8 (C). ESI-MS: m=z 406 [M þ H]þ.

3174
P. SAHA ET AL.
Data for Compound 5a
Rf(30% petroleum ether–EtOAc) 0.50. Grey solid; mp 80-82oC. 1H NMR
(600 MHz, CDCl3): d 4.00 (2H, s), 5.19 (1H, d, J ¼ 0.6 Hz), 5.37 (1H, d, J ¼ 1.2 Hz),
5.60 (2H, s), 7.10 (2H, m), 7.20 (2H, m), 7.33 (1H, s), 7.43 (1H, m), 8.41 (1H, dd,
J1 ¼ 7.8 Hz, J2 ¼ 1.2 Hz), 8.97 (1H, dd, J1 ¼ 4.2 Hz, J2 ¼ 1.2 Hz); 13C NMR (CDCl3,
150 MHz): d 41.3 (CH2), 75.7 (CH2), 114.8 (CH2), 121.4 (CH), 125.0 (CH), 126.1 (C),
127.6 (CH), 128.5 (CH), 128.7 (CH), 132.4 (CH), 132.9 (CH), 133.1 (C), 134.1 (C),
142.2 (C), 143.4 (C), 148.5 (C), 150.1 (CH), 150.3 (C), 151.2 (C). ESI-MS: m=z
308 [M þ H]þ, 330 [M þ Na]þ, HRMS: calcd. 308.0842 [M þ H]þ; found 308.0836.
Data for Compound 5b
Rf(30% petroleum ether–EtOAc) 0.42. Greenish yellow solid; mp 72–74oC. 1H
NMR (600 MHz, CDCl3): d 2.78 (3H, s, J ¼ 3.6 Hz), 3.98 (2H, s), 5.11 (1H, s), 5.32
(1H, d, J ¼ 1.2 Hz), 5.57 (2H, s), 7.07 (1H, m), 7.09 (1H, m), 7.18 (4H, m), 7.33 (1H,
d, J ¼ 8.4 Hz), 7.90 (1H, d, J ¼ 8.4 Hz). 13C NMR (CDCl3, 150 MHz): d 25.7 (CH3),
41.5 (CH2), 75.7 (CH2), 114.0 (CH2), 121.6 (CH), 122.5 (CH), 126.6 (C), 127.2
(CH), 127.9 (CH), 128.0 (CH), 128.2 (CH), 128.5 (CH), 132.8 (C), 135.1(C), 135.9
(CH), 142.5 (C), 142.6 (C), 149.6 (C), 151.8 (C), 158.5 (C). ESI-MS: m=z 288
[M þ H]þ, HRMS: calcd. 288.1388 [M þ H]þ; found 288.1383.
Data for Compound 5c
Rf(25% petroleum ether–EtOAc) 0.40. Pale yellow solid; mp 94–96oC. 1H NMR
(600 MHz, CDCl3): d 4.02 (2H, s), 5.19 (1H, s), 5.37 (1H, s), 5.62 (2H, s), 7.11 (2H, m),
7.19 (2H, m), 7.43 (3H, m), 8.07 (1H, d, J ¼ 7.8 Hz), 8.96 (1H, brs). 13C NMR (CDCl3,
150 MHz): d 41.4 (CH2), 75.6 (CH2), 114.6 (CH2), 120.7 (CH), 120.8 (CH), 122.6
(CH), 127.5 (C), 127.7 (CH), 127.9 (CH), 128.7 (CH), 128.9 (CH), 129.4 (CH),
132.4 (C), 136.4 (C), 137.9 (CH), 142.5 (C), 149.1 (C), 149.5 (C), 151.8 (C). ESI-MS:
m=z 274 [M þ H]þ, HRMS: calcd. 274.1232 [M þ H]þ; found 274.1227.
Data for Compound 5d
Rf(30% petroleum ether–EtOAc) 0.52. Grey solid; mp 76–78oC. 1H NMR
(600 MHz, CDCl3): d 3.79 (3H, s), 4.10 (2H, s), 5.23 (1H, d, J ¼ 1.2 Hz), 5.42 (1H,
d, J ¼ 1.8 Hz), 5.68 (2H, s), 7.06 (2H, m), 7.27 (1H, s), 7.39 (1H, s), 7.47 (1H, m),
8.32 (1H, dd, J1 ¼ 7.2 Hz, J2 ¼ 0.6 Hz), 8.92 (1H, dd, J1 ¼ 3.6 Hz, J2 ¼ 1.2 Hz); 13C
NMR (CDCl3, 150 MHz): d 42.4 (CH2), 56.5 (CH3), 75.9 (CH2), 115.4 (CH2),
121.0 (CH), 122.2 (CH), 127.1 (CH), 128.9 (CH), 129.4 (CH), 132.7 (CH), 133.3
(C), 133.9 (CH), 134.6 (C), 143.0 (C), 143.9 (C), 148.7 (C), 150.0 (C), 150.9 (C),
151.8 (C), 159.4 (C). ESI-MS: m=z 338 [M þ H]þ, 360 [M þ Na]þ.
Data for Compound 5e
1
Rf(30% petroleum ether–EtOAc) 0.58. Light brown solid; mp 94–96oC. H
NMR (600 MHz, CDCl3): d 4.09 (2H, s), 5.27 (1H, d, J ¼ 0.6 Hz), 5.50 (1H, s),

FUSED TETRACYCLIC BENZOXOCINOQUINOLINC
3175
5.73 (2H, s), 7.20 (1H, s), 7.23 (1H, m), 7.31 (1H, s), 7.45 (1H, s), 7.51 (1H, m), 8.32
(1H, m), 8.96 (1H, dd, J1 ¼ 2.4 Hz, J2 ¼ 0.6 Hz); 13C NMR (CDCl3, 150 MHz): d 42.5
(CH2), 75.7 (CH2), 115.0 (CH2), 120.3 (CH), 122.6 (CH), 127.7 (CH), 128.7 (CH),
129.0 (CH), 132.5 (CH), 133.0 (CH), 133.7 (C), 134.3 (C), 143.2 (C), 144.0 (C),
148.5 (C), 150.4 (C), 152.0 (C), 152.8 (C), 159.9 (C). ESI-MS: m=z 326 [M þ H]þ,
348 [M þ Na]þ.
CONCLUSION
In conclusion, we have developed
a
new methodology for basic
alumina-supported microwave-assisted intramolecular Heck reaction and exempli-
fied it by the synthesis of eight-membered benzoxocinoquinoline. The operational
simplicity, energy efficiency, and general applicability of the strategy coupled with
the reusability of basic alumina ensure the development of green methodology for
further syntheses of other heterocyclic compounds of interest.
ACKNOWLEDGMENTS
We thank the Council of Scientific and Industrial Research (CSIR), New Delhi,
for financial support in the form of fellowships to P. Saha, S. Mondal, A. Hazra, S.
Naskar, A. Maity, K. B. Sahu, and R. Paira. We are also thankful to B. Achari,
emeritus scientist, CSIR, for suggestions and encouragement. Our special thanks
go to B. C. Ranu of Indian Association for the Cultivation of Science (IACS),
Kolkata, for his generous cooperation in utilizing the microwave instrument.
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