Synthesis of pyrrolo[2,1-a]isoquinolines from activated acetylenes, benzoylnitromethanes, and isoquinoline

Article abstract of DOI:10.1016/j.tet.2009.01.001

Isoquinoline reacts smoothly with aroylnitromethanes in the presence of dialkyl acetylenedicarboxylates and dibenzoylacetylene to produce pyrrolo[2,1-a]isoquinolines in good yields. Quinoline and benzothiazole also react in a similar way. Pyridine and N-m

Full text of DOI:10.1016/j.tet.2009.01.001

Tetrahedron 65 (2009) 2067–2071
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Synthesis of pyrrolo[2,1-a]isoquinolines from activated acetylenes,
benzoylnitromethanes, and isoquinoline
,
b
,
a
b
Issa Yavari a , Mohammad Piltan , Loghman Moradi
*
a Chemistry Department, Science & Research Campus, Islamic Azad University, Ponak, Tehran, Iran
b Chemistry Department, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 27 July 2008
Received in revised form 2 December 2008
Accepted 5 January 2009
Available online 8 January 2009
Isoquinoline reacts smoothly with aroylnitromethanes in the presence of dialkyl acetylenedicarboxylates
and dibenzoylacetylene to produce pyrrolo[2,1-a]isoquinolines in good yields. Quinoline and benzo-
thiazole also react in a similar way. Pyridine and N-methylimidazole catalyze the reaction between ni-
tromethane derivatives with electron-deficient acetylenes to produce highly functionalized isoxazoles.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Pyrroloisoquinoline
Benzoylnitromethane
Activated acetylenes
N-Heterocycles
Isoxazoles
1. Introduction
2. Results and discussion
In recent years, nitroalkanes have proved to be very useful
building blocks for the one-pot synthesis of a variety of important
targets. A one-pot process can be planned by the right choice of
different parameters such as (i) reaction conditions, (ii) catalyst, (iii)
addition sequence of reactants, or (iv) use of starting materials with
a high chemical versatility, e.g., nitroalkanes. Nitroalkanes are
a valuable source of stabilized carbanions since the high electron-
withdrawing power of the nitro group provides an outstanding
The reaction of isoquinoline (1) with dialkyl acetylenedi-
carboxylates (2a–d) or dibenzoylacetylene (2e) in the presence of
aroylnitromethanes (3) proceeded smoothly in H2O/MeCN (5:1)
mixture and was complete within 3 h. The 1H and 13C NMR spectra
of the crude products clearly indicated the formation of pyr-
rolo[2,1-a]isoquinolines (4a–g) in 71–85% yields (Table 1).
The structures of compounds 4a–g were deduced from their IR,
1H NMR, and 13C NMR spectra. For example, the 1H NMR spectrum
enhancement of the hydrogen acidity at the
a
-position.1–5 Nitro-
of 4a exhibited signals for methoxy (
d
¼3.48 and 3.90 ppm) protons,
nate anions can be generated from nitroalkanes using a wide range
of bases and act as carbon nucleophiles with common electrophiles,
including aldehydes6,7 and electron-poor alkenes,8 leading to car-
bon–carbon bond formation. The nitro group can be removed from
the molecule by replacing it with hydrogen9,10 or by elimination as
nitrous acid, introducing a double bond.11,12
As part of our current interest in the application of nitroalkanes
in organic synthesis,13–16 we describe a simple synthesis of func-
tionalized pyrrolo[2,1-a]isoquinolines, pyrrolo[1,2-a]quinoline,
pyrrolo[2,1-b][1,3]benzothiazole, and highly functionalized isox-
azole derivatives. The reaction forming fused pyrroles is comple-
mentary to the cycloadditions of quinolinium and isoquinolinium
ylides with electron-deficient acetylenes.17
along with multiplets (d¼7.16–9.18 ppm) for the aromatic region.
The proton-decoupled 13C NMR spectrum of 4a showed 21 distinct
resonances in agreement with the proposed structure. The IR
spectrum of 4a displayed characteristic carbonyl bands (1735, 1732,
and 1680 cmꢀ1). The 1H NMR and 13C NMR spectra of 4b–g were
similar to those for 4a except for the ester moieties, which
exhibited characteristic resonances in the appropriate regions of
the spectrum. The tribenzol derivative 4g is reported before.
However, the melting point reported18 for 4g (218–220 ꢁC) is far
from 135–137 ꢁC of the present paper.
Although the mechanistic details of the reaction are not known,
a plausible rationalization may be advanced to explain the product
formation (Scheme 1). Presumably, the zwitterionic inter-
mediate19–21 formed from isoquinoline and 2 is protonated by 3 to
furnish intermediate 6, which is attacked by carbanion 7 to produce
8. This intermediate undergoes a series of cyclization and elimi-
nation reactions to generate product 4.
* Corresponding author. Tel.: þ98 21 82886631; fax: þ98 21 82883455.
E-mail address: yavarisa@modares.ac.ir (I. Yavari).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.001

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I. Yavari et al. / Tetrahedron 65 (2009) 2067–2071
Table 1
Reaction of isoquinoline (1) with activated acetylenic compounds 2 in the presence of aroylnitromethanes 3 in aqueous media
Entry
Activated acetylene
Nitro compound
Product
Yielda/%
O
N
MeO2C
CO2Me
CO2Me
CO2Me
NO2
a
80
PhOC
4a
2a
3a
O
O
N
EtO2C
CO2Et
CO2Et
CO2Et
NO2
b
78
75
76
2b
PhOC
3a
4b
i
i
C
CO
PrO2
2 Pr
NO2
NO2
N
i
CO2 Pr
c
PhOC
PhOC
i
CO2 Pr
2c
3a
4c
O
t
t
Bu O2C
CO2Bu
N
t
CO2 Bu
d
t
CO2 Bu
2d
4d
3a
O
NO2
N
MeO2C
CO2Me
CO2Me
CO2Me
4e
e
75
2a
O
3b
O
NO2
N
EtO2C
PhOC
CO2Et
CO2Et
CO2Et
f
71
85
2b
O
3b
4f
O
N
COPh
NO2
COPh
COPh
g
2e
PhOC
3a
4g
a
Yield after recrystallization.
NO2
COR
COR
+
COR
COR
3
+
N
H
N
N
1 + 2
COPh
PhOC
NO2 COR
COR
5
6
7
8
NO2
N
_
_
N
HNO2
COR
COR
H2
Cyclization
COR
4
PhOC
PhOC
COR
9
10
Scheme 1. Proposed mechanism for the formation of compounds 4.

I. Yavari et al. / Tetrahedron 65 (2009) 2067–2071
2069
Under similar reaction conditions, DMAD reacts with benzoyl-
nitromethane in the presence of quinoline and benzothiazole to
produce dimethyl 3-benzoylpyrrolo[1,2-a]quinoline-1,2-dicarboxy-
late (11) and dimethyl 3-benzoylpyrrolo[2,1-b][1,3]benzothiazole-
1,2-dicarboxylate (12) (Scheme 2). Compounds 11 and 12 were
again fully characterized according to their elemental analyses and
their IR, 1H NMR, and 13C NMR spectra.
500 AVANCE instrument; in CDCl3 at 500.1 and 125.7 MHz, re-
spectively; in parts per million, J in hertz. EIMS: Finnigan-MAT-
8430 mass spectrometer, at 70 eV; in m/z. Elemental analyses:
d
Heraeus CHN-O-Rapid analyzer.
3.2. General procedure for the synthesis of functionalized
pyrrolo[2,1-a]isoquinolines 4
To a stirred solution of 2 (2 mmol) and 3 (2 mmol) in 5 mL of
H2O/MeCN (5:1) was added isoquinoline (0.26 g, 2 mmol) at rt. The
reaction mixture was then stirred for 3 h. The precipitates were
filtered and recrystallized from methanol to give 4.
MeO2C
CO2Me
N
COPh
N
COPh
12(56%)
MeO2C
11
S
CO2Me
(63%)
3.2.1. Dimethyl 1-benzoylpyrrolo[2,1-a]isoquinoline-2,3-
dicarboxylate (4a)
Pale yellow crystals, mp 196–198 ꢁC, 0.62 g, yield 80%. IR (KBr)
Scheme 2.
(
nmax/cmꢀ1): 1735 (C]O), 1732 (C]O), 1680 (C]O), 1641, 1366,
1210. MS, m/z (%): 387 (Mþ, 10), 310 (100), 284 (10), 105 (30), 77
To extend our knowledge of this reaction, we performed the
reaction between DMAD and nitromethane derivatives 13 in the
presence of pyridine and N-methylimidazole in H2O/MeCN (5:1)
mixture. Surprisingly, this reaction led to functionalized isoxazoles
14a–g in good yields (Scheme 3). Pyridine and N-methylimidazole
act as a catalyst in this transformation and the reaction proceeds
smoothly at rt in the presence of 20 mol % of the catalyst. Recently,
we reported16 the synthesis of similar isoxazoles through the re-
action of activated acetylenes and alkyl 2-nitroethanoates in the
presence of triphenylphosphine under reflux condition in tolu-
ene.13 However, pyridine and N-methylimidazole are found to be
more effective catalysts for formation of isoxazoles 14 in aqueous
media.
(60). Anal. Calcd for C23H17NO5 (387.38): C, 71.31; H, 4.42; N,
3.62%. Found: C, 71.78; H, 4.54; N, 3.78%. 1H NMR:
d 3.48 (3H, s,
OMe), 3.90 (3H, s, OMe), 7.16 (1H, d, 3J¼7.6 Hz, CH), 7.33 (1H, t,
3J¼7.5 Hz, CH), 7.41 (2H, t, 3J¼7.5 Hz, 2CH), 7.47 (1H, t, 3J¼7.0 Hz,
CH), 7.54 (1H, t, 3J¼7.0 Hz, CH), 7.65 (1H, d, 3J¼7.8 Hz, CH), 7.87
(2H, d, 3J¼7.5 Hz, 2CH), 8.04 (1H, d, 3J¼8.3 Hz, CH), 9.18 (1H, d,
3J¼7.6 Hz, CH) ppm. 13C NMR:
d 52.0 (OMe), 52.1 (OMe), 114.2 (C),
115.6 (CH), 117.0 (C), 123.9 (CH), 124.1 (C), 125.2 (CH), 127.0 (C),
127.2 (CH), 128.0 (CH), 128.5 (2CH), 128.6 (CH), 129.0 (C), 129.7
(2CH), 132.0 (C), 133.3 (CH), 138.4 (C), 160.8 (C]O), 164.8 (C]O),
193.4 (C]O) ppm.
3.2.2. Diethyl 1-benzoylpyrrolo[2,1-a]isoquinoline-2,3-
dicarboxylate (4b)
COR
Pale yellow crystals, mp 137–139 ꢁC, 0.65 g, yield 78%. IR (KBr)
ROC
ROC
COR'
Pyridine or
O
+
(
nmax/cmꢀ1): 1736 (C]O), 1732 (C]O), 1684 (C]O), 1640, 1398,
N-Methylimidazole
NO2
N
R'
1203. MS, m/z (%): 415 (Mþ, 5), 338 (100), 312 (15), 105 (35), 77 (62).
H2O/MeCN (5:1)
O
COR
Anal. Calcd for C25H21NO5 (415.44): C, 72.28; H, 5.09; N, 3.37%.
2
R
Yield/%
13
R
R'
R'
OMe
OEt
Ph
14
a
Found: C, 72.61; H, 5.20; N, 3.48%. 1H NMR:
d
1.06 (3H, t, 3J¼7.2 Hz,
a
b
c
d
OMe
OEt
a
b
c
OMe OMe 85
Me), 1.33 (3H, t, 3J¼7.2 Hz, Me), 3.91 (2H, q, 3J¼7.2 Hz, OCH2), 4.36
(2H, q, 3J¼7.2 Hz, OCH2), 7.16 (1H, d, 3J¼7.6 Hz, CH), 7.33 (1H, t,
3J¼8.1 Hz, CH), 7.41 (2H, t, 3J¼7.8 Hz, 2CH), 7.47 (1H, t, 3J¼7.5 Hz,
CH), 7.53 (1H, t, 3J¼7.4 Hz, CH), 7.66 (1H, d, 3J¼7.9 Hz, CH), 7.90 (2H,
d, 3J¼8.1 Hz, 2CH), 8.04 (1H, d, 3J¼8.3 Hz, CH), 9.22 (1H, d,
b
OMe OEt 70
t
O Bu
c
OEt
OEt 75
O Bu OEt 71
Ph OEt 65
OMe Ph
Ph Ph
t
Ph
d
e
f
70
71
g
3J¼7.6 Hz, CH) ppm. 13C NMR:
d 13.7 (Me), 14.0 (Me), 61.1 (OCH2),
Scheme 3. Synthesis of compounds 14.
61.5 (OCH2), 114.3 (C), 115.4 (CH), 116.7 (C), 124.0 (CH), 124.2 (C),
125.2 (CH), 127.2 (CH), 127.3 (C), 128.0 (CH), 128.5 (2CH), 128.6 (CH),
129.1 (C), 129.9 (2CH), 131.9 (C), 133.4 (CH), 138.4 (C), 160.4 (C]O),
164.5 (C]O), 193.4 (C]O) ppm.
A synthesis of compound 14f from benzoylnitromethane and
DMAD in refluxing xylene in the presence of a catalytic amount of
p-toluenesulfonic acid is reported22 before; the melting point and
spectroscopic data are in good agreement with our results.
In summary, we have reported a transformation involving iso-
quinoline, activated acetylenes, and benzoylnitromethane to pro-
duce pyrrolo[2,1-a]isoquinolines in good yields. Quinoline and
benzothiazole also react in a similar way. Alternatively, pyridine
and N-methylimidazole catalyzed the reaction between nitro-
methane derivatives with electron-deficient acetylenes to produce
highly functionalized isoxazoles.
3.2.3. Diisopropyl 1-benzoylpyrrolo[2,1-a]isoquinoline-2,3-
dicarboxylate (4c)
Yellow crystals, mp 150–152 ꢁC, 0.66 g, yield 75%. IR (KBr)
(
nmax/cmꢀ1): 1726 (C]O), 1723 (C]O), 1682 (C]O), 1648, 1376,
1213. MS, m/z (%):443 (Mþ, 6), 366 (100), 340 (12), 105 (20), 77
(57). Anal. Calcd for C27H25NO5 (443.49): C, 73.12; H, 5.68; N,
3.16%. Found: C, 73.42; H, 5.53; N, 3.38%. 1H NMR:
d 1.05 (6H, d,
3J¼6.3 Hz, CHMe2), 1.38 (6H, d, 3J¼6.5 Hz, CHMe2), 4.80–4.85 (1H,
m, CH), 5.28–5.33 (1H, m, CH), 7.16 (1H, d, 3J¼7.6 Hz, CH), 7.35
(1H, t, 3J¼7.5 Hz, CH), 7.44 (2H, t, 3J¼7.8 Hz, 2CH), 7.47 (1H, t,
3J¼7.8 Hz, CH), 7.49 (1H, t, 3J¼7.7 Hz, CH), 7.58 (1H, d, 3J¼7.8 Hz,
CH), 7.96 (2H, d, 3J¼7.2 Hz, 2CH), 7.89 (1H, d, 3J¼7.8 Hz, CH), 9.25
3. Experimental
3.1. General
(1H, d, 3J¼7.6 Hz, CH) ppm. 13C NMR:
d 21.3 (CHMe2), 21.8
Dibenzoylacetylene was prepared by a known procedure.23,24
The reagents and solvents used in this work were obtained from
Aldrich and Fluka and were used without further purification. Mp:
Electrothermal-9100 apparatus. IR Spectra: Shimadzu IR-460
spectrometer; in cmꢀ1. 1H NMR and 13C NMR spectra: Bruker DRX-
(CHMe2), 69.1 (CHMe2), 69.5 (CHMe2), 114.2 (C), 115.0 (C), 115.1
(CH), 123.5 (CH), 124.1 (C), 125.1 (CH), 127.1 (C), 127.2 (CH), 128.0
(CH), 128.4 (2CH), 128.6 (C), 129.1 (2CH), 130.0 (C), 131.2 (CH),
133.6 (CH), 138.2 (C), 160.1 (C]O), 164.0 (C]O), 193.4
(C]O) ppm.

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I. Yavari et al. / Tetrahedron 65 (2009) 2067–2071
3.2.4. Di(tert-butyl) 1-benzoylpyrrolo[2,1-a]isoquinoline-2,3-
dicarboxylate (4d)
136.1 (CH), 142.4 (C), 152.1 (C), 159.8 (C), 164.9 (C), 180.8 (C]O),
184.2 (C]O), 186.5 (C]O) ppm.
Yellow crystals, mp 164–166 ꢁC, 0.71 g, yield 76%. IR (KBr) (nmax
/
cmꢀ1): 1723 (C]O), 1717 (C]O), 1681 (C]O), 1659, 1368, 1201. MS,
m/z (%): 471 (Mþ, 9), 394 (100), 368 (14), 105 (31), 77 (59). Anal.
Calcd for C29H29NO5 (471.55): C, 73.87; H, 6.20; N, 2.97%. Found: C,
3.3. General procedure for the synthesis of compounds
11 and 12
74.08; H, 6.03; N, 3.16%. 1H NMR:
d
1.28 (9H, s, CMe3), 1.58 (9H, s,
To a stirred solution of 2a (0.28 g, 2 mmol) and 3a (2 mmol) in
5 mL of H2O/MeCN (5:1) was added quinoline or benzothiazole
(2 mmol) at rt. The reaction mixture was then stirred for 5 h. The
precipitates were filtered and recrystallized from methanol to give
the title compounds.
CMe3), 7.00 (1H, d, 3J¼7.6 Hz, CH), 7.25 (1H, t, 3J¼7.7 Hz, CH), 7.37
(1H, t, 3J¼7.9 Hz, CH), 7.39 (2H, t, 3J¼7.6 Hz, 2CH), 7.52 (1H, t,
3J¼7.7 Hz, CH), 7.57 (1H, d, 3J¼7.7 Hz, CH), 7.82 (1H, d, 3J¼8.3 Hz,
CH), 7.96 (2H, d, 3J¼7.5 Hz, 2CH), 9.10 (1H, d, 3J¼7.6 Hz, CH) ppm.
13C NMR:
d 27.3 (CMe3), 28.1 (CMe3), 82.0 (CMe3), 82.6 (CMe3), 114.6
(CH), 116.4 (C), 116.5 (C), 123.8 (CH), 124.2 (C), 124.4 (CH), 126.1 (C),
127.0 (CH), 127.8 (CH), 127.9 (CH), 128.6 (C), 128.7 (2CH), 129.9
(2CH), 130.2 (C), 133.6 (CH), 138.0 (C), 160.1 (C]O), 162.4 (C]O),
193.9 (C]O) ppm.
3.3.1. Dimethyl 3-benzoylpyrrolo[1,2-a]quinoline-1,2-
dicarboxylate (11)
Pale yellow powder, mp 100–102 ꢁC, 0.49 g, yield 63%. IR (KBr)
(
nmax/cmꢀ1): 1734 (C]O), 1730 (C]O), 1681 (C]O), 1643, 1356,
1205. MS, m/z (%): 387 (Mþ, 8), 310 (100), 284 (11), 105 (36), 77
3.2.5. Dimethyl 1-(4-methyl)benzoylpyrrolo[2,1-a]isoquinoline-
2,3-dicarboxylate (4e)
(68). Anal. Calcd for C23H17NO5 (387.38): C, 71.31; H, 4.42; N,
3.62%. Found: C, 71.39; H, 4.57; N, 3.77%. 1H NMR:
d 3.72 (3H, s,
Pale yellow crystals, mp 207–209 ꢁC, 0.60 g, yield 75%. IR (KBr)
OMe), 4.03 (3H, s, OMe), 7.43 (1H, d, 3J¼7.5 Hz, CH), 7.45 (2H, t,
3J¼7.5 Hz, 2CH), 7.48 (1H, t, 3J¼7.5 Hz, 2CH), 7.50 (1H, t, 3J¼7.6 Hz,
CH), 7.77 (1H, t, 3J¼8.1 Hz, CH), 7.80 (1H, d, 3J¼8.2 Hz, 1CH), 7.87
(1H, d, 3J¼8.1 Hz, 2CH), 8.10 (2H, d, 3J¼7.7 Hz, 2CH), 8.21 (1H, d,
(
nmax/cmꢀ1): 1732 (C]O), 1729 (C]O), 1692 (C]O), 1637, 1361,
1213. MS, m/z (%): 401 (Mþ, 6), 324 (100), 298 (10), 105 (20), 77
(70). Anal. Calcd for C24H19NO5 (401.41): C, 71.81; H, 4.77; N,
3.49%. Found: C, 71.78; H, 4.54; N, 3.78%. 1H NMR:
d
2.43 (3H, s,
3J¼7.5 Hz, CH) ppm. 13C NMR:
d 51.8 (OMe), 53.2 (OMe), 117.5 (C),
Me), 3.56 (3H, s, OMe), 3.94 (3H, s, OMe), 7.18 (1H, d, 3J¼7.5 Hz,
CH), 7.25 (2H, d, 3J¼7.6 Hz, 2CH), 7.37 (1H, t, 3J¼7.5 Hz, 1CH), 7.50
(1H, t, 3J¼7.3 Hz, CH), 7.68 (1H, d, 3J¼7.7 Hz, CH), 7.83 (2H, d,
3J¼7.6 Hz, 2CH), 8.05 (1H, d, 3J¼7.4 Hz, 1CH), 9.21 (1H, d,
117.7 (CH), 121.1 (CH), 125.4 (C), 125.8 (CH), 125.9 (C), 126.7 (CH),
128.3 (C), 128.4 (2CH), 128.8 (C), 128.9 (2CH), 129.1 (CH), 129.2 (C),
129.6 (CH), 129.9 (CH), 130.5 (C), 159.9 (C]O), 163.4 (C]O), 191.3
(C]O) ppm.
3J¼7.5 Hz, CH) ppm. 13C NMR:
d 22.2 (Me), 52.5 (OMe), 52.7
(OMe), 114.7 (C), 116.0 (CH), 117.8 (C), 124.4 (CH), 124.8 (C), 125.7
(CH), 127.3 (C), 127.7 (CH), 128.6 (CH), 129.1 (CH), 129.6 (C), 129.7
(2CH), 130.4 (2CH), 132.3 (C), 136.4 (C), 144.9 (C), 161.4 (C]O),
165.4 (C]O), 193.6 (C]O) ppm.
3.3.2. Dimethyl 3-benzoylpyrrolo[2,1-b][1,3]benzothiazole-1,2-
dicarboxylate (12)
Pale yellow powder, mp 100–102 ꢁC, 0.44 g, yield 56%. IR (KBr)
(
nmax/cmꢀ1): 1722 (C]O), 1719 (C]O), 1679 (C]O), 1654, 1355,
1200. MS, m/z (%): 393 (Mþ, 9), 316 (100), 290 (20),105 (28), 77 (57).
3.2.6. Diethyl 1-(4-methyl)benzoylpyrrolo[2,1-a]isoquinoline-2,3-
dicarboxylate (4f)
Anal. Calcd for C21H15NO5S (393.41): C, 64.11; H, 3.84; N, 3.56%.
Found: C, 64.36; H, 3.65; N, 3.68%. 1H NMR:
d 3.53 (3H, s, OMe), 3.93
Pale yellow crystals, mp 165–167 ꢁC, 0.61 g, yield 71%. IR (KBr)
(3H, s, OMe), 7.45 (2H, t, 3J¼7.7 Hz, CH), 7.49 (1H, t, 3J¼7.7 Hz, CH),
7.52 (1H, t, 3J¼7.7 Hz, CH), 7.69 (2H, d, 3J¼8.4 Hz, 2CH), 7.72 (1H, t,
3J¼7.7 Hz, CH), 7.87 (1H, d, 3J¼7.7 Hz, CH), 8.95 (1H, d, 3J¼8.3 Hz,
(
nmax/cmꢀ1): 1733 (C]O), 1732 (C]O), 1683 (C]O), 1638, 1362,
1211. MS, m/z (%): 429 (Mþ, 8), 352 (100), 326 (14), 105 (25), 77 (65).
Anal. Calcd for C26H23NO5 (429.44): C, 72.72; H, 5.36; N, 3.26%.
CH) ppm. 13C NMR:
d 51.8 (OMe), 51.9 (OMe), 117.6 (C), 123.0 (C),
Found: C, 72.68; H, 5.27; N, 3.48%. 1H NMR:
d
1.12 (3H, t, 3J¼7.3 Hz,
125.2 (CH), 126.3 (C), 127.9 (2CH), 128.7 (2CH), 129.0 (C), 129.9 (CH),
131.2 (CH),132.9 (C),133.1 (C),134.4 (CH),138.3 (CH),142.5(C),159.6
(C]O), 164.2 (C]O), 188.8 (C]O) ppm.
Me), 1.45 (3H, t, 3J¼7.3 Hz, Me), 2.40 (3H, s, Me), 3.90 (2H, q,
3J¼7.3 Hz, OCH2), 4.06 (2H, q, 3J¼7.3 Hz, OCH2), 7.19 (1H, d,
3J¼7.5 Hz, CH), 7.27 (2H, d, 3J¼7.6 Hz, 2CH), 7.35 (1H, t, 3J¼7.5 Hz,
1CH), 7.48 (1H, t, 3J¼7.3 Hz, CH), 7.61 (1H, d, 3J¼7.7 Hz, CH), 7.80
(2H, d, 3J¼7.6 Hz, 2CH), 8.10 (1H, d, 3J¼7.4 Hz, 1CH), 9.23 (1H, d,
3.4. General procedure for the synthesis of functionalized
isoxazoles 14
3J¼7.5 Hz, CH) ppm. 13C NMR:
d 13.9 (Me), 14.4 (Me), 22.4 (Me), 61.1
(OCH2), 62.3 (OCH2),114.8 (C),116.1 (CH),118.7 (C), 124.6 (CH),125.0
(C), 125.4 (CH), 126.9 (C), 127.6 (CH), 128.4 (CH), 128.9 (CH), 129.3
(C), 129.9 (2CH), 131.3 (2CH), 131.9 (C), 135.4 (C), 144.7 (C), 160.8
(C]O), 164.9 (C]O), 192.8 (C]O) ppm.
To a stirred solution of 2 (2 mmol) and 13 (2 mmol) in 5 mL of
H2O/MeCN (5:1) was added pyridine or N-methylimidazole
(20 mol %) at rt. The reaction mixture was then stirred for 6 h. The
solvent was removed under reduced pressure and the viscous
residue was purified by column chromatography (Merck 230–400
mesh) using n-hexane/EtOAc (4:1) as eluent. Compounds 14a–e are
reported previously.16
3.2.7. 1,2,3-Tribenzoylpyrrolo[2,1-a]isoquinoline (4g)
Pale yellow crystals, mp 135–137 ꢁC, 0.81 g, yield 85%. IR (KBr)
(
nmax/cmꢀ1): 1674 (C]O), 1640 (C]O), 1593 (C]O), 1232, 958, 557.
MS, m/z (%): 479 (Mþ, 10), 402 (100), 376 (16), 105 (33), 77 (63).
3.4.1. Dimethyl 3-benzoyl-isoxazole-4,5-dicarboxylate (14f)
Anal. Calcd for C33H21NO3 (479.53): C, 82.66; H, 4.41; N, 2.92%.
Pale yellow powder, mp 91–93 ꢁC [lit.22 88–89 ꢁC] 0.41 g, yield
70%. IR (KBr) (nmax/cmꢀ1): 1746 (C]O), 1743 (C]O), 1738 (C]O),
1646, 1580, 1282. MS, m/z (%): 289 (Mþ, 10), 212 (100), 186 (22), 105
(57), 77 (75). Anal. Calcd for C14H11NO6 (289.24): C, 58.14; H, 3.83;
Found: C, 82.88; H, 4.54; N, 3.06%. 1H NMR:
d
7.54 (2H, t, 3J¼7.7 Hz,
2CH), 7.57–7.63 (4H, m, 4CH), 7.68 (1H, t, 3J¼7.4 Hz, CH), 7.74–7.80
(3H, m, 3CH), 7.84 (1H, d, 3J¼7.2 Hz, CH), 7.88 (2H, d, 3J¼8.3 Hz, CH),
7.97 (1H, d, 3J¼8.2 Hz, CH), 8.06 (2H, d, 3J¼8.3 Hz, 2CH), 8.15 (1H, d,
3J¼8.1 Hz, CH), 8.17 (2H, d, 3J¼7.3 Hz, 2CH), 8.52 (1H, d, 3J¼7.5 Hz,
N, 4.84%. Found: C, 59.78; H, 5.60; N, 6.98%. 1H NMR:
d 3.87 (3H, s,
OMe), 4.00 (3H, s, OMe), 7.50 (2H, t, 3J¼6.6 Hz, 2CH), 7.65 (1H, t,
CH), 9.33 (1H, d, 3J¼7.4 Hz, CH) ppm. 13C NMR:
d
115.4 (C), 123.8 (C),
3J¼6.8 Hz, CH), 8.13 (2H, d, 3J¼7.17 Hz, 2CH) ppm. 13C NMR:
d 53.2
126.3 (CH), 127.1 (C), 125.5 (C), 128.7 (2CH), 128.9 (2CH), 129.0
(2CH), 129.2 (2CH), 129.8 (2CH), 130.0 (C), 130.3 (2CH), 130.7 (CH),
134.2 (CH),134.4 (CH),134.5 (CH), 134.9 (CH),135.1 (CH),135.2 (CH),
(OMe), 53.6 (OMe), 117.6 (C), 128.8 (2CH), 130.5 (2CH), 134.8 (CH),
134.9 (C), 155.9 (C), 159.1 (C), 159.9 (C]O), 160.1 (C]O), 183.7
(C]O) ppm.

I. Yavari et al. / Tetrahedron 65 (2009) 2067–2071
5. Adams, J. P. J. Chem. Soc., Perkin Trans. 1 2002, 2586.
2071
3.4.2. 3,4,5-Tribenzoyl-isoxazole (14g)
6. Rosini, G. In Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon:
Oxford, 1991; Vol. 2, p 321.
7. Luzzio, F. A. Tetrahedron 2001, 57, 915.
8. Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri, A.; Petrini, M. Chem. Rev. 2005, 105,
933.
9. Ono, N.; Miyake, H.; Tamura, R.; Kaji, A. Tetrahedron Lett. 1981, 22, 1705.
10. Rosini, G.; Ballini, R.; Zanotti, V. Synthesis 1983, 137.
11. Ballini, R.; Bosica, G. Tetrahedron 1995, 51, 4213.
White powder, mp 145–147 ꢁC, 0.53 g, yield 80%. IR (KBr) (nmax
/
cmꢀ1): 1670, 1647, 1569, 1250, 870, 673. MS, m/z (%): 381 (Mþ, 12),
304 (100), 278 (26), 105 (50), 77 (82). Anal. Calcd for C24H15NO4
(381.38): C, 75.58; H, 3.96; N, 3.67%. Found: C, 75.77; H, 3.80; N,
3.78%. 1H NMR:
d
7.43 (2H, t, 3J¼7.8 Hz, 2CH), 7.51–7.59 (5H, m,
5CH), 7.66–7.69 (2H, m, 2CH), 7.85 (2H, d, 3J¼7.3 Hz, 2CH), 8.12 (2H,
d, 3J¼7.4 Hz, 2CH), 8.28 (2H, d, 3J¼7.4 Hz, 2CH) ppm. 13C NMR:
12. Ballini, R.; Petrini, M. Tetrahedron 2004, 60, 1017.
13. Yavari, I.; Moradi, L.; Mokhtarporyani-Sanandaj, A.; Mirzaei, A. Helv. Chim. Acta
2007, 90, 392.
d
125.3 (C), 128.7 (2CH), 128.8 (2CH), 128.9 (2CH), 129.1 (2CH), 130.1
(2CH), 130.7 (2CH), 133.9 (CH), 134.6 (C), 134.7 (CH), 134.8 (CH),
134.9 (C), 136.5 (C), 160.6 (C), 165.0 (C), 180.3 (C]O), 183.6 (C]O),
186.9 (C]O) ppm.
14. Yavari, I.; Moradi, L. Helv. Chim. Acta 2006, 89, 1942.
15. Yavari, I.; Moradi, L.; Mirzaei, A. Helv. Chim. Acta 2006, 89, 2918.
16. Yavari, I.; Moradi, L. Tetrahedron Lett. 2006, 47, 1627.
17. Acheson, R. M.; Elmore, N. F. Adv. Heterocycl. Chem. 1978, 23, 407.
18. Wei, X.; Hu, Y.; Li, T.; Hu, H. Synth. Commun. 1992, 22, 2103.
19. Huisgen, R.; Morikawa, M.; Herbig, K.; Brunn, E. Chem. Ber. 1967, 100, 1094.
20. Winterfeldt, E.; Schumann, D.; Dillinger, H. J. Chem. Ber. 1969, 102, 1656.
21. Dillinger, H. J.; Fengler, G.; Schumann, D.; Winterfeldt, E. Tetrahedron 1974, 30,
2553 and 2561.
22. Shimizu, T.; Hayashi, Y.; Teramura, K. Bull. Chem. Soc. Jpn. 1984, 57, 2531.
23. Skattebøl, L.; Jones, E. R. H.; Whiting, M. C. Org. Synth. Coll. Vol. 4, 1963, 792.
24. Bowden, K.; Heilborn, I. M.; Jones, E. R. H.; Weedon, B. C. L. J. Chem. Soc.
1946, 39.
References and notes
1. Rosini, G.; Ballini, R. Synthesis 1988, 833.
2. Ono, N. The Nitro Group in Organic Synthesis; Wiley: New York, NY, 2001.
3. Nitro Compounds: Recent Advances in Synthesis and Chemistry; Feuer, H., Nielsen,
A. T., Eds.; Wiley-VCH: Weinheim, 1990.
4. The Chemistry of Amino, Nitroso, Nitro and Related Groups; Patai, S., Ed.; Wiley:
Chichester, UK, 1996.