Simple and efficient access to 3-ethoxycarbonylpyrroles, naphthofurans

Article abstract of DOI:10.1055/s-0029-1217053

An efficient method was developed for the synthesis of pyrrole and furan derivatives from enamines, phenols, and naphthols. The key steps involve iodocyclization and alumina-induced dehydroiodination reactions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217053

PAPER
3963
Simple and Efficient Access to 3-Ethoxycarbonylpyrroles, Benzofurans, and
Naphthofurans
3
-Ethoxycarbony
a
lpyrroles,
B
m
enzofurans, and
N
a
i
phthof
l
urans a G. Pancote,a Bruno S. de Carvalho,b Cibele V. Luchez,b João P. S. Fernandes,a Mario J. Politi,b
Carlos A. Brandt*c
a
Departamento de Farmácia, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil
Instituto Butantan,, Av. Vital Brazil 1500, 05503-900 São Paulo, SP, Brazil
b
c
E-mail: cabrandt@usp.br
Received 29 April 2009; revised 11 August 2009
keto ester 2 by the method that we previously described,9
Abstract: An efficient method was developed for the synthesis of
followed by treatment with iodine, afforded the corre-
pyrrole and furan derivatives from enamines, phenols, and naph-
thols. The key steps involve iodocyclization and alumina-induced
dehydroiodination reactions.
sponding (iodomethyl)dihydropyrroles derivatives 4 in
excellent yields. Finally, reaction of the iodo derivatives
with neutral alumina at 150 °C gave the required pyrrole
derivatives 5 in good yields (Scheme 1).
Key words: alumina, dehydroiodination, heterocycles, iodocy-
clization, ultrasound
O
O
O
O
LiOH⋅H2O
Pyrrole and furan derivatives are important classes of
five-membered heterocycles found in many natural prod-
ucts.1,2 They have attracted much attention because of
their broad spectrum of pharmacological activities, in-
cluding antineoplastic,3 antipsychotic,4 antimicrobial, an-
tioxidant, and anti-retroviral activities.5 These compounds
can be readily prepared by iodine-promoted cyclization of
functionally substituted alkenes.6,7 For example, we have
previously reported a synthesis of pyrroles by iodocy-
clization of b-enamino esters followed by elimination.6
However, the new demand for synthetic routes that are
rapid, inexpensive, and environmentally safe must be con-
sidered. In seeking more-efficient methods, we decide to
try adapting a method that we previously developed for
the synthesis of pyrroles.6 First, we found that ultrasound
promotes the alkylation of ethyl acetoacetate enolates
with allyl bromide. This procedure, which can be per-
formed without a solvent, satisfies the demands of envi-
ronmentally benign green chemistry. Because of the
recent popularity of organic transformations under
RNH2
OEt
Br
OEt
OEt
, )))
AcOH, )))
1
2 (90%)
O
O
NHR
O
OEt
OEt
Al2O3
I2
I
150 °C
15 min
r.t.
24 h
N
R
N
R
3a R = Ph, 60%
3b R = Bn, 98%
3c R = n-Hex, 92%
4a R = Ph, 75%
5a R = Ph, 80%
4b R = Bn, 85%
5b R = Bn, 85%
4c R = n-Hex, 80%
5c R = n-Hex, 80%
Scheme 1 Synthesis of 3-ethoxycarbonylpyrroles
The dehydroiodination reaction can be carried out without
a solvent and the reaction mixture must be treated with an
organic solvent that is capable of dissolving the organic
materials; alumina is therefore suitable as both a support
and a reactant because it can be easily removed by filtra-
tion at the end of the preparation and recycled.
solvent-free conditions, we also examined the dehydro- The method was also used for the synthesis of benzo-
iodination of the intermediate products on alumina in the furans and naphthofuran derivatives. Thus, reaction of
absence of a solvent. Benzofurans and naphthofurans phenols 6,10 and 911 and naphthols 1212 and 1510 with io-
were similarly prepared by the same protocol.
dine, followed by treatment with alumina with heating
gave the corresponding products 8,13 11,14 14,15 and 17,7
respectively (Scheme 2 and Scheme 3).
The required starting material, ethyl 2-acetylpent-4-
enoate (2), was prepared by alkylation of ethyl acetoace-
tate (1) with allyl bromide in the presence of lithium hy- Finally, this method was extended to the synthesis of 2,4-
droxide monohydrate and water in an ultrasound bath at dimethylfuro[3,2-c]quinoline (20).16 3-Allyl-2-methyl-
room temperature. Our process resulted in an improve- quinolin-4-ol (18), which we recently prepared,17 under-
ment in the concentration and yields of monoalkyl prod- went iodocyclization to give dihydrofuran derivative 1911
ucts in comparison with all other methods that use various in excellent yield. Dehydroiodination of 19, as described
organic solvents.8 The condensation of amines with b- above, gave the desired product, as shown in Scheme 4.
As shown in Scheme 5, we propose that an intermediate A
may be involved in the reaction; because of its basic char-
acter, alumina may abstract a proton to give an exometh-
SYNTHESIS 2009, No. 23, pp 3963–3966
Advanced online publication: 19.10.2009
x
x.
x
x
.
2
0
0
9
DOI: 10.1055/s-0029-1217053; Art ID: M02309SS
© Georg Thieme Verlag Stuttgart · New York

3964
C. G. Pancote et al.
PAPER
ylene intermediate B, which aromatizes to give the strategy very attractive for the synthesis of this very im-
product C.
portant group of heterocyclic compounds, which can
serve key intermediates for the synthesis of several bio-
logically active products.
The simplicity of the whole process, the ready availability
of starting materials, and the high overall yield make this
I
1H NMR and 13C NMR spectra were recorded with a Bruker
DPX300 spectrometer operating at 300 MHz and 75 MHz, respec-
tively, in CDCl3 as a solvent with TMS as an internal standard.
Chemical shifts are reported in parts per million (ppm, d units).
Coupling constants are reported in units of hertz (Hz), if applicable.
IR spectra were recorded with a Bomem MB100-FTIR spectrome-
ter, measured in percentage of transmittance (% T) on samples pre-
pared as films or KBr pellets. All GC/MS studies were performed
on a Shimadzu 14B/QP5050A with a DB1 column (30 m). For liq-
uid chromatography, 70–230 mesh silica gel (Merck) was used as
the stationary phase.
OH
O
O
I2
Al2O3
r.t.
24 h
150 °C
15 min
OMe
OMe
OMe
6
7 (87%)
8 (82%)
I
OH
O
O
Me
MeO
MeO
Al2O3
I2
O
150 °C
15 min
r.t.
24 h
Ethyl-2-acetylpent-4-enoate (2)
A mixture of ethyl acetoacetate (1; 10.5 mmol), LiOH (10.5 mmol),
H2O (2 mL), and allyl bromide (10.0 mmol) was placed in an ultra-
sound bath (USC 700, 40 KHz) for 15 min. The mixture was then
extracted with EtOAc (20 mL), dried (anhyd Na2SO4), and concen-
trated. For technical reasons, the products from three independent
reactions were combined and purified by fractional distillation at
115 °C/16 mm Hg; yield: 4.60 g (90%).
CHO
CHO
CHO
9
10 (90%)
11 (80%)
Scheme 2 Synthesis of benzofurans 8 and 11
I
OH
O
O
Iodocyclization; General Procedure
I2
Al2O3
A soln of the substituted alkene derivative (5 mmol) in CH2Cl2 (25
mL) was treated with NaHCO3 (5.5 mmol) and I2 (5.5 mmol). The
mixture was stirred at r.t. for 24 h then extracted with EtOAc. The
combined organic layers were washed sequentially with aq Na2S2O3
and sat. aq NaCl, dried (MgSO4), and concentrated under reduced
pressure.
r.t.
24 h
150 °C
15 min
12
13 (80%)
14 (81%)
I
O
O
OH
Ethyl 5-(Iodomethyl)-2-methyl-1-phenyl-4,5-dihydro-1H-pyr-
I2
Al2O3
role-3-carboxylate (4a)
Yield: 75%.
1H NMR (300 MHz, CDCl3): d = 1.30 (t, J = 7.3 Hz, 3 H), 2.08 (s,
3 H), 2.65 (dd, J = 8.0, 15.1 Hz, 1 H), 3.05 (dd, J = 10.0, 15.1 Hz, 1
H), 3.15 (dd, J = 3.0, 10.5 Hz, 1 H), 3.25 (dd, J = 7.3, 10.5 Hz, 1 H),
4.15 (q, J = 7.3 Hz, 2 H), 4.05–4.20 (m, 1 H), 7.10–7.45 (m, 5 H).
r.t.
150 °C
15 min
24 h
15
16 (80%)
17 (85%)
Scheme 3 Synthesis of naphthofurans 14 and 17
13C NMR (75 MHz, CDCl3): d = 11.3, 13.9, 14.5, 35.1, 58.5, 64.2,
98.5, 126.8, 127.5, 129.5, 140.2, 157.5, 166.7.
OH
NH
O
250 °C
I2
Ethyl 1-Benzyl-5-(iodomethyl)-2-methyl-4,5-dihydro-1H-pyr-
role-3-carboxylate (4b)
OEt
r.t.
24 h
N
Yield: 85%.
3a
18 (75%)
1H NMR (300 MHz, CDCl3): d = 1.27 (t, J = 7.1 Hz, 3 H), 2.29 (s,
3 H), 2.53 (dd, J = 7.2, 15.1 Hz, 1 H), 3.04 (dd, J = 11.2, 15.1 Hz, 1
H), 3.10–3.20 (m, 2 H), 3.54–3.67 (m, 1 H), 4.15 (q, 7.1 Hz, 2 H),
4.25 (d, J = 16.8 Hz, 1 H), 4.52 (d, J = 16.8 Hz, 1 H), 7.14–7.35 (m,
5 H).
13C NMR (75 MHz, CDCl3): d = 10.9, 12.3, 14.6, 35.2, 47.9, 58.6,
60.7, 95.7, 126.7, 127.5, 128.8, 137.1, 159.6, 166.9.
I
O
N
O
N
Al2O3
150 °C
15 min
19 (85%)
20 (90%)
Scheme 4 Synthesis of 2,4-dimethylfuro[3,2-c]quinoline (20)
Ethyl 1-Hexyl-5-(iodomethyl)-2-methyl-4,5-dihydro-1H-pyr-
role-3-carboxylate (4c)
Yield: 80%.
IR (film): 1687, 1585, 1239, 1081 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.89 (t, J = 6.9 Hz, 3 H), 1.25 (t,
J = 7.1 Hz, 3 H), 1.25–1.38 (m, 6 H), 1.50–1.60 (m, 2 H), 2.05 (s, 3
H), 2.50 (dd, J = 7.5, 15.0 Hz, 1 H), 3.00 (dd, J = 11.0, 15.0 Hz, 1
H), 3.08–3.17 (m, 2 H), 3.20 (t, J = 7.0 Hz, 2 H), 4.00–4.13 (m, 1
H), 4.15 (q, 7.1 Hz, 2 H).
X
X
X
R1
R2
R1
R2
R1
R2
I
H
alumina
X = O, NR
B
C
A
Scheme 5 Proposed reaction mechanism
Synthesis 2009, No. 23, 3963–3966 © Thieme Stuttgart · New York

PAPER
3-Ethoxycarbonylpyrroles, Benzofurans, and Naphthofurans
3965
13C NMR (75 MHz, CDCl3): d = 11.3, 12.3, 13.8, 14.1, 22.4, 26.5,
27.4, 31.0, 35.9, 43.6, 59.2, 61.4, 110.1, 157.9, 166.9.
Anal. Calcd for C11H11IO3: C, 41.53; H, 3.49. Found: C, 41.68; H,
3.54.
Anal. Calcd for C15H26NO2I: C, 47.50; H, 6.91; N, 3.69. Found: C,
47.66; H, 6.88; N, 3.74.
Dehydroiodination; General Procedure
Neutral activated Al2O3 (Merck 70–230 mesh; 30 g) was added to a
stirred solution of the cyclic iodine derivative (1 mmol) in CH2Cl2
(20 mL). The solvent was removed under vacuum, and the mixture
was heated at 160 °C for 15 min then cooled to r.t. CH2Cl2 (10 mL)
was added, the Al2O3 was removed by Büchner filtration, and the
organic phase was evaporated under vacuum.
2-(Iodomethyl)-5-methoxy-2,3-dihydro-1-benzofuran (7)
Yield: 87%.
1H NMR (300 MHz, CDCl3): d = 3.15 (dd, J = 6.9, 15.9 Hz, 1 H),
3.22–3.45 (m, 3 H), 3.74 (s, 3 H), 4.80–4.92 (m, 1 H), 6.79 (dd,
J = 2.7, 8.9 Hz, 1 H), 6.94 (d, J = 2.7 Hz, 1 H), 7.27 (d, J = 8.9 Hz,
1 H).
Ethyl 2,5-Dimethyl-1-phenyl-1H-pyrrole-3-carboxylate (5a)
Yield: 80%.
IR (KBr): 1685, 1582, 1420, 1220, 1090 cm–1.
13C NMR (75 MHz, CDCl3): d = 9.1, 36.5, 56.0, 81.8, 109.5, 111.4,
113.1, 126.7, 153.3, 154.4.
1H NMR (300 MHz, CDCl3): d = 1.31 (t, J = 7.3 Hz, 3 H), 1.97 (s,
3 H), 2.28 (s, 3 H), 4.28 (q, J = 7.3 Hz, 2 H), 6.38 (s, 1 H), 7.10–7.55
(m, 5 H).
13C NMR (75 MHz, CDCl3): d = 12.1, 12.6, 14.3, 58.9, 107.5,
111.5, 128.0, 128.4, 128.7, 129.5, 136.0, 137.7, 165.6.
2-(Iodomethyl)-2,3-dihydronaphtho[1,2-b]furan (13)
Yield: 80%.
1H NMR (300 MHz, CDCl3): d = 3.22 (dd, J = 6.5, 15.9 Hz, 1 H),
3.41 (dd, J = 7.8, 10.0 Hz, 1 H), 3.55 (dd, J = 4.7, 10.0 Hz, 1 H),
3.58 (dd, J = 9.3, 15.9 Hz, 1 H), 5.05–5.15 (m, 1 H), 7.30 (d, J = 8.2
Hz, 1 H), 7.39 (d, J = 8.2 Hz, 1 H), 7.40–7.46 (m, 2 H), 7.80 (d,
J = 8.0 Hz, 1 H), 7.93 (d, J = 8.0 Hz, 1 H).
Anal. Calcd for C15H17NO2: C, 74.05; H, 7.04; N, 5.76. Found: C,
73.89; H, 6.92; N, 5.69.
13C NMR (75 MHz, CDCl3): d = 9.2, 36.9, 82.3, 118.7, 120.4,
120.7, 121.3, 122.7, 125.4, 125.8, 127.8, 133.5, 154.4.
Ethyl 1-Benzyl-2,5-dimethyl-1H-pyrrole-3-carboxylate (5b)
Yield: 85%.
2-(Iodomethyl)-1,2-dihydronaphtho[2,1-b]furan (16)
IR (KBr): 1701, 1692, 1606, 1581 cm–1.
Yield: 80%.
1H NMR (300 MHz, CDCl3): d = 1.29 (t, J = 7.1 Hz, 3 H), 2.09 (s,
3 H), 2.45 (s, 3 H), 4.26 (q, J = 7.1 Hz, 2 H), 5.01 (s, 2 H), 6.35 (s,
1 H), 6.85–7.32 (m, 5 H).
13C NMR (75 MHz, CDCl3): d = 11.1, 11.9, 14.4, 46.6, 59.0, 107.6,
111.0, 125.4, 127.2, 127.8, 128.7, 135.3, 136.9, 165.5.
1H NMR (300 MHz, CDCl3): d = 3.31 (dd, J = 8.7, 15.7 Hz, 1 H),
3.39–3.55 (m, 2 H), 3.67 (dd, J = 9.5, 15.7 Hz, 1 H), 5.05–5.14 (m,
1 H), 7.10 (d, J = 8.8 Hz, 1 H), 7.32 (t, J = 8.2 Hz, 1 H), 7.48 (t,
J = 8.2 Hz, 1 H), 7.59 (d, J = 8.8 Hz, 1 H), 7.70 (d, J = 8.2 Hz, 1 H),
7.81 (d, J = 8.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 9.2, 35.1, 82.4, 112.0, 122.7,
123.1, 126.8, 128.7, 128.9, 129.3, 129.4, 130.7, 156.7.
Ethyl 1-Hexyl-2,5-dimethyl-1H-pyrrole-3-carboxylate (5c)
Yield: 80%.
IR (KBr): 1697, 1580, 1230, 1085 cm–1.
2-(Iodomethyl)-4-methyl-2,3-dihydrofuro[3,2-c]quinoline (19)
Yield: 85%.
IR (KBr): 1644, 1592, 1550, 1505, 1331, 1158 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.02 (s, 3 H), 3.26 (dd, J = 6.5,
15.9 Hz, 1 H), 3.57–3.68 (m, 2 H), 3.66 (dd, J = 10.0, 15.9 Hz, 1 H),
5.38–5.48 (m, 1 H), 7.70 (t, J = 8.6, 1 H), 7.92 (t, J = 8.6 Hz, 1 H),
8.03 (d, J = 8.6 Hz, 1 H), 8.84 (d, J = 8.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 12.1, 23.1, 35.2, 84.4, 115.7,
117.2, 121.9, 126.1, 128.3, 130.1, 148.4, 156.3, 162.5.
1H NMR (300 MHz, CDCl3): d = 0.89 (t, J = 6.9 Hz, 3 H), 1.29–
1.34 (m, 6 H), 1.31 (t, J = 7.1 Hz, 3 H), 1.50–1.65 (m, 2 H), 2.19 (s,
3 H), 2.51 (s, 3 H), 3.73 (t, J = 6.9 Hz, 2 H), 4.23 (q, J = 7.1 Hz, 2
H), 6.24 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 11.4, 14.0, 14.6, 22.6, 26.5, 26.9,
30.6, 31.5, 43.7, 59.1, 107.4, 119.2, 127.3, 132.2, 165.8.
Anal. Calcd for C15H25NO2: C, 71.67; H, 10.03; N, 5.57. Found: C,
71.82; H, 9.83; N, 5.45.
Anal. Calcd for C13H13INO: C, 48.02; H, 3.72; N, 4.31. Found: C,
47.92; H, 3.83; N, 4.25.
5-Methoxy-2-methyl-1-benzofuran (8)
Yield: 82%.
1H NMR (300 MHz, CDCl3): d = 2.42 (d, J = 1.0 Hz, 3 H), 3.82 (s,
3 H), 6.30 (q, J = 1.0 Hz, 1 H), 6.79 (dd, J = 2.6, 8.9 Hz, 1 H), 6.94
(d, J = 2.6 Hz, 1 H), 7.28 (d, J = 8.9 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.2, 58.5, 102.8, 103.1, 110.9,
111.3, 129.8, 149.7, 155.7, 156.3.
Iodocyclization of 3-Allyl-4-hydroxy-5-methoxybenzaldehyde
(9)
The procedure was the same as the general procedure, except that a
1:1 mixture of H2O and MeOH was used as the solvent.
2-(Iodomethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-carbal-
dehyde (10)
Yield: 90%.
IR (film): 2715, 1705, 1655, 1580, 1105 cm–1.
7-Methoxy-2-methyl-1-benzofuran-5-carbaldehyde (11)
Yield: 80%.
IR (KBr): 2715, 1715, 1660, 1573, 1110 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.39 (d, J = 0.8 Hz, 3 H), 3.98 (s,
3 H), 6.75 (q, J = 0.8 Hz, 1 H), 7.28 (s, 1 H), 7.35 (s, 1 H), 9.92 (s,
1 H).
13C NMR (75 MHz, CDCl3): d = 14.3, 56.2, 101.9, 118.2, 123.5,
128.6, 129.5, 148.5, 154.8, 156.6, 191.5.
1H NMR (300 MHz, CDCl3): d = 3.16 (dd, J = 7.0, 16.1 Hz, 1 H),
3.41 (dd, J = 7.9, 10.3 Hz, 1 H), 3.50 (dd, J = 9.1, 16.1 Hz, 1 H),
3.53 (dd, J = 4.1, 10.3 Hz, 1 H), 3.94 (s, 3 H), 5.00–5.06 (m, 1 H),
7.33 (s, 1 H), 7.35 (s, 1 H), 9.81 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 9.1, 36.2, 56.0, 82.1, 110.4, 126.5,
126.8, 129.2, 149.1, 153.8, 190.7.
Anal. Calcd for C11H10O3: C, 69.46; H, 5.30. Found: C, 69.33; H,
5.38.
Synthesis 2009, No. 23, 3963–3966 © Thieme Stuttgart · New York

3966
C. G. Pancote et al.
PAPER
2-Methylnaphtho[1,2-b]furan (14)
Yield: 81%.
1H NMR (300 MHz, CDCl3): d = 2.52 (d, J = 1.0 Hz, 3 H), 6.45 (q,
J = 1.0 Hz, 1 H), 7.40 (t, J = 8.1 Hz, 1 H), 7.52 (t, J = 8.1 Hz, 1 H),
7.53 (d, J = 8.5 Hz, 1 H), 7.58 (d, J = 8.5 Hz, 1 H), 7.87 (d, J = 8.1
Hz, 1 H), 8.24 (d, J = 8.1 Hz, 1 H).
(2) (a) Yin, G.; Wang, Z.; Chen, A.; Gao, M.; Wu, A.; Pan, Y.
J. Org. Chem. 2008, 73, 3377; and references cited therein.
(b) Da Silva, F. C.; Fonseca, M. G.; Rianelli, R. S.; Cunha,
A. C.; De Souza, M. C. B. V.; Ferreira, V. F. Beilstein J.
Org. Chem. 2008, 4, 45; and references cited therein.
(3) (a) Gangjee, A.; Devraj, R.; McGuire, J. J.; Kisliuk, R. L.
J. Med. Chem. 1995, 38, 3798. (b) Palimbar, S. S.; More, V.
S.; Srinivasan, K. V. Ultrason. Sonochem. 2008, 15, 853.
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Agents, In Burger’s Medicinal Chemistry and Drug
Discovery, 6th ed., Vol. 6; Abraham, D. J., Ed.; Wiley:
Hoboken, 2003, 599. (b) De Oliveira, E. O.; Brandt, C. A.;
Da Silveira, M. A. B.; Glennon, R. A. Tetrahedron Lett.
2007, 48, 6393.
(5) (a) Maeda, S.; Masuda, H.; Tokoroyama, T. Chem. Pharm.
Bull. 1994, 42, 2536. (b) Rida, S. M.; El-Hawash, S. A. M.;
Fahmy, H. T. Y.; Hazzaa, A. A.; El-Meligy, M. M. M. Arch.
Pharm. Res. 2006, 29, 826. (c) Hayakawa, I.; Shioya, R.;
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L.; Ragauskas, A. J. Tetrahedron 2007, 63, 10958.
(6) Ferraz, H. M. C.; De Oliveira, E. O.; Payret-Arrua, M. E.;
Brandt, C. A. J. Org. Chem. 1995, 60, 7357.
13C NMR (75 MHz, CDCl3): d = 14.1, 103.6, 119.2, 119.6, 121.2,
122.9, 124.4, 124.5, 126.1, 128.3, 130.8, 149.8, 154.8.
2-Methylnaphtho[2,1-b]furan (17)
Yield: 85%.
1H NMR (300 MHz, CDCl3): d = 2.52 (d, J = 1.1 Hz, 3 H), 6.45 (q,
J = 1.1 Hz, 1 H), 7.41 (t, J = 8.2 Hz, 1 H), 7.53 (t, J = 8.2 Hz, 1 H),
7.54 (d, J = 8.5 Hz, 1 H), 7.59 (d, J = 8.5 Hz, 1 H), 7.88 (d, J = 8.2
Hz, 1 H), 8.25 (d, J = 8.2 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.3, 103.2, 118.1, 118.5, 121.8,
122.3, 125.2, 125.7, 128.5, 129.0, 130.1, 150.2, 154.4.
2,4-Dimethylfuro[3,2-c]quinoline (20)
Yield: 90%.
IR (KBr): 1658, 1589, 1520, 1250 cm–1.
(7) Yadav, A. K.; Singh, B. K.; Singh, N.; Tripathi, R. P.
Tetrahedron Lett. 2007, 48, 6628.
1H NMR (300 MHz, CDCl3): d = 2.53 (d, J = 1.1 Hz, 3 H), 2.80 (s,
3 H), 6.48 (q, J = 1.1 Hz, 1 H), 7.51 (t, J = 8.0 Hz, 1 H), 7.61 (t,
J = 8.0 Hz, 1 H), 8.09 (d, J = 8.0 Hz, 1 H), 8.14 (d, J = 8.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.2, 23.2, 106.5, 116.2, 120.1,
121.9, 126.9, 128.5, 129.5, 145.3, 154.4, 154.1, 156.3.
(8) For a similar reaction, see: Antonioletti, R.; Bonadies, F.;
Orelli, L. R.; Scettri, A. Gazz. Chim. Ital. 1992, 122, 237.
(9) Brandt, C. A.; Da Silva, A. C. M. P.; Pancote, C. G.; Brito,
C. L.; Da Silveira, M. A. B. Synthesis 2004, 1557.
(10) Tsang, K. Y.; Brimble, M. A. Tetrahedron 2007, 63, 6015.
(11) Pancote, C. G. Dissertation; University of São Paulo: Brazil,
2009.
Anal. Calcd for C13H11NO: C, 79.16; H, 5.62; N, 7.10. Found: C,
79.12; H, 5.69; N, 7.15.
(12) Majundar, K. C.; Chattopadhyay, B.; Singh, N.; Ray, K.
Tetrahedron Lett. 2007, 48, 7633.
Acknowledgment
(13) Salom-Roig, X. J.; Renaud, P. Synthesis 2006, 3419.
(14) Ishii, H.; Ishikawa, T.; Wada, H.; Miyakaki, H.; Kaneko, Y.;
Harayama, T. Chem. Pharm. Bull. 1992, 40, 2614.
(15) Feldman, K. S.; Perkins, A. L. Tetrahedron Lett. 2001, 42,
6031.
(16) Avetisyan, A. A.; Aleksanyan, I. L.; Pivazyan, A. A. Zh.
Org. Khim. 2006, 42, 755; Russ. J. Org. Chem. (Engl.
Transl.) 2006, 42, 739.
(17) Tempone, A. G.; Da Silva, A. C. M. P.; Brandt, C. A.;
Martinez, F. S.; Borborema, S. E. T.; Da Silveira, M. A. B.;
Andradre, H. F. Jr. Antimicrob. Agents Chemother. 2005, 49,
1076.
Thanks to Conselho Nacional de Desenvolvimento Científico e
Tecnológico (CNPq, Brazil), Fundação de Amparo à Pesquisa do
Estado de São Paulo (FAPESP), and Coordenação de Aperfeiçoa-
mento de Pessoal de Nível Superior (CAPES) for their financial
support of this work.
References
(1) Joule, J. A.; Mills, K. Heterocyclic Chemistry, 4th ed;
Blackwell Science: Malden, 2008.
Synthesis 2009, No. 23, 3963–3966 © Thieme Stuttgart · New York