A synthetic route to 11-(1H-pyrrol-1-yl)-11H-indeno[1,2-b]quinoxaline derivatives exploiting a three-component coupling strategy under microwave irradiation

Article abstract of DOI:10.1016/j.tetlet.2005.06.099

11H-Indeno[1,2-b]quinoxalin-11-ones generated in situ from ninhydrin and various 1,2-phenylenediamines, catalysed by montmorillonite K10 under microwave irradiation, condense with 4-hydroxyproline to produce 11-(1H-pyrrol-1-yl)-11H- indeno[1,2-b]quinoxaline derivatives in good yields.

Full text of DOI:10.1016/j.tetlet.2005.06.099

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6155–6157
A synthetic route to 11-(1H-pyrrol-1-yl)-
11H-indeno[1,2-b]quinoxaline derivatives exploiting a
three-component coupling strategy under microwave irradiation
Javad Azizian,* Ali Reza Karimi, Zahra Kazemizadeh,
Ali A. Mohammadi and Mohammad R. Mohammadizadeh
Department of Chemistry, Faculty of Science, Shahid Beheshti University, PO Box 19395-4716, Tehran, Iran
Received 25 February 2005; revised 10 June 2005; accepted 21 June 2005
Abstract—11H-Indeno[1,2-b]quinoxalin-11-ones generated in situ from ninhydrin and various 1,2-phenylenediamines, catalysed by
montmorillonite K10 under microwave irradiation, condense with 4-hydroxyproline to produce 11-(1H-pyrrol-1-yl)-11H-
indeno[1,2-b]quinoxaline derivatives in good yields.
Ó 2005 Published by Elsevier Ltd.
One-pot multicomponent processes have recently gained
considerable and steadily increasing academic, economic
and ecological interest because they address fundamen-
tal principles of synthetic efficiency and reaction design.1
Additionally, the prospect of extending one-pot reac-
tions into combinatorial and solid-phase synthesis1,2
promises many opportunities for developing novel lead
structures for pharmaceuticals, catalysts and even novel
molecule based materials.
report a novel, efficient and three-component method
for the construction of 11-(1H-pyrrol-1-yl)-11H-indeno-
[1,2-b]quinoxalines, via condensation of ninhydrin,
1,2-phenylenediamine and 4-hydroxyproline catalysed
by montmorillonite K10 under microwave irradiation.
The multicomponent diversity elements are introduced
by simple addition of 1equiv of a 1,2-phenylenediamine
to 1equiv of ninhydrin on montmorillonite K10, then
five drops of DMSO were added followed by 4-hydroxy-
proline (1equiv) and the mixture exposed to MW to
afford the corresponding 11-(1H-pyrrol-1-yl)-11H-
indeno[1,2-b]quinoxalines 4 (Scheme 1).
Since the pyrrole subunit occurs in many medicines, pes-
ticides and natural products, the development of new
methodologies3–7 for the synthesis of pyrroles is of inter-
est. Indenoquinoxaline8 derivatives are an important
class of intermediates in organic synthesis.
The results were excellent in terms of yields and product
purity in the presence of montmorillonite K10, while
without it, only the 11H-indeno[1,2-b]quinoxalin-11-
one 5 and 4-hydroxyproline were recovered (Table 1).
This indicates that a catalyst is needed for this reaction.
In the context of our general interest in multiple compo-
nent reactions9 and as part of our ongoing research pro-
grammes in the area of pyrrole synthesis,9c,10 herein we
N
O
1
R
HO
NH2
NH2
OH
OH
montmorillonite K10
N
+
+
2
DMSO/ MW
R1
R2
COOH
R
N
H
N
O
1
2a-c
3
4a-c
Scheme 1.
Keywords: Three-component reaction; Pyrroles; Microwave irradiation.
*
Corresponding author. Tel.: +98 212990 2895; fax: +98 12 5348 40547; e-mail: j-azizian@cc.sbu.ac.ir
0040-4039/$ - see front matter Ó 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2005.06.099

6156
J. Azizian et al. / Tetrahedron Letters 46 (2005) 6155–6157
Table 1.
fers could then give azomethine ylide 9, that is, 4a
(Scheme 2).
K 10
Time
(min)
Products 4
Yield
(%)
MP
(°C)
In order to prove the presence of the intermediate
5 in the proposed mechanism, compound 5 was
synthesised separately by condensation of ninhydrin
1 and 1,2-phenylenediamine 2a, and then the reaction
of 5 and 3 was examined. The resulting product was
identical to that formed in the three-component
procedure.
N
0.5 g
—
2
6
82
—
N
1
80
N
4a
N
In summary, the multicomponent reaction described
herein provides a simple and direct entry into a number
of interesting novel pyrroles.
0.2 g
—
2
6
78
—
N
N
1
92
CH3
N
4b
4c
General procedure: Montmorillonite K10 (0.2 g) was
placed in a mortar followed by ninhydrin (0.178 g,
1mmol) and 1,2-phenylenediamine (0.108 g, 1mmol)
to which was added five drops of DMSO. The reactants
were mixed for 5 min. To this mixture was then added
4-hydroxyproline (0.130 g, 1 mmol). These materials
were then mixed using a pestle for ca. 5 min. The
homogenised mixture was placed in a pyrex test tube
and inserted into a microwave oven and irradiated for
2 min. The contents were cooled to room temperature
and mixed thoroughly with 10 mL of acetone. The solid
inorganic material was filtered off, water was added and
the separated solid was filtered off and dried under high
vacuum and recrystallised from ethanol to give the pure
crystalline solid 4a (0.235 g).
N
0.5 g
—
2
6
80
—
CH
3
231
N
CH
3
The 1H NMR spectrum of 4a exhibited one single sharp
line at (d 6.21) readily recognised as arising from a
methine proton along with multiplets (d 7.58–8.29) for
the aromatic protons. Two triplets (d 6.23 and 6.74)
were identified as pyrrole ring protons because of the
small coupling constants of the protons characteristic
1
of five-membered pyrrole rings (J = 2.10 Hz). The H
decoupled 13C NMR spectrum of 4a showed 17 distinct
resonances in agreement with the proposed structure.
The signal at 61.63 ppm corresponds to the methine car-
bon. The signals at 109.30 and 120.40 ppm are consis-
tent with the presence of a pyrrole ring.11
References and notes
We have not yet established a mechanism for the forma-
tion of 4a–c, but a reasonable possibility is indicated in
Scheme 2.
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First, condensation of ninhydrin and 1,2-phenylene-
diamine would give 11H-indeno[1,2-b]quinoxalin-11-one
5. This would undergo condensation with 4-hydroxy-
proline to form azomethine ylide 7 by thermal decarboxy-
lation of 6. The azomethine ylide 7 would dehydrate
spontaneously to produce the conjugated azomethine
ylide 8, catalysed by montmorillonite K10. Proton trans-
2. Kobayashi, S. Chem. Soc. Rev. 1999, 28, 1–15.
3. For a review on the synthesis of pyrroles, see: Ferreira, V.
F.; Souza, M. C. B. V.; Cunha, A. C.; Pereira, L. O. R.;
O
HO
O
O
HO
NH2
OH
N
O
+
N
+
N
COOH
OH
N
NH2
H
N
O
N
1
2a
5
3
6
HO
N
N
N
N
1,5 -H shift
-H O
-CO
2
2
N
N
N
N
N
N
N
N
7
8
9
4a
Scheme 2.

J. Azizian et al. / Tetrahedron Letters 46 (2005) 6155–6157
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9. (a) Azizian, J.; Mohammadi, A. A.; Karimi, A. R.;
Mohammadizadeh, M. R. J. Org. Chem. 2005, 70, 350–
352; (b) Azizian, J.; Karimi, A. R.; Mohammadi, A. A.
Synth. Commun. 2003, 33, 383–387; (c) Azizian, J.;
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130.34, 130.38, 132.19, 137.19, 141.67, 142.59, 143.80,
153.17, 158.16 (arom). MS(EI) (m/z, %): 283 (M+, 100), 217
(85), 190 (60), 141 (15), 114 (15), 89 (45), 63 (16), 39 (50).
Anal. Calcd for C19H13N3: C, 80.54; H, 4.62; N, 14.83.
Found: C, 80.58; H, 4.63; N, 14.81.
8-Methyl-11-(1H-pyrrol-1-yl)-11H-indeno[1,2-b]quinoxa-
line 4b: mp: 192 °C, IR (KBr) (mmax, cmÀ1): 3098, 2918,
1483; 1H NMR (CDCl3, 300 MHz) dH: 2.66 (3H, s, CH3),
6.25 (1H, s, CH), 6.27 (2H, br s, CHpyrrole), 6.74 (2H, t,
J = 2.00 Hz, CHpyrrole), 7.62–8.23 (7H, m, arom); 13C
NMR (CDCl3, 75 MHz) dC: 22.08 (CH3), 62.13 (CH),
109.55, 120.44 (2CHpyrrole), 122.58, 124.70, 128.69, 130.45,
131.13, 132.55, 136.70, 141.14, 141.38, 142.88, 143.88,
148.42, 153.17, 158.16 (arom). MS(EI) (m/z, %): 297 (M+,
30), 246 (100), 231 (55), 218 (60), 190 (15), 130 (15), 89
(30). Anal. Calcd for C20H15N3: C, 80.78; H, 5.08; N,
14.13. Found: C, 80.77; H, 5.05; N, 14.11.
7,8-Dimethyl-11-(1H-pyrrol-1-yl)-11H-indeno[1,2-b]quino-
xaline 4c: mp: 231 °C, IR (KBr) (mmax, cmÀ1): 3120, 2915,
1486, 1329; 1H NMR (CDCl3, 500 MHz) dH: 2.44 and
2.47 (6H, 2s, 2CH3), 6.12 (1H, s, CH), 6.23 (2H, t, J =
1.50 Hz, CHpyrrole), 6.73 (2H, t, J = 1.56 Hz, CHpyrrole),
7.50–8.19 (6H, m, arom); 13C NMR (CDCl3, 125 MHz)
dC: 20.23 and 20.35 (2CH3), 61.66 (CH), 109.17, 120.37
(2CHpyrrole), 122.29, 125.83, 128.33, 129.00, 130.16,
131.54, 137.67, 139.72, 140.50, 140.65, 141.60, 143.56,
152.37, 157.14 (arom). MS(EI) (m/z, %): 311 (M+, 100), 245
(90), 229 (30), 103 (15), 77 (15), 39 (45). Anal. Calcd for
C21H17N3: C, 81.00; H, 5.50; N, 13.49. Found: C, 79.88;
H, 5.55; N, 13.51.
10. Azizian, J.; Karimi, A. R.; Kazemizadeh, Z.; Moham-
madi, A. A.; Mohammadizadeh, M. R. J. Org. Chem.
2005, 70, 1471–1473.
11. Spectral data for products: 11-(1H-Pyrrol-1-yl)-11H-
indeno[1,2-b]quinoxaline 4a: mp: 180 °C, IR (KBr) (mmax
,
cmÀ1): 3095, 2920, 1478; 1H NMR (CDCl3, 500 MHz) dH:
6.21(1H, s, CH), 6.23 (2H, t, J = 2.10 Hz, CHpyrrole), 6.74
(2H, t, J = 2.09 Hz, CHpyrrole), 7.58–8.29 (8H, m, arom);
13C NMR (CDCl3, 75 MHz) dC: 61.63 (CH), 109.30,
120.40 (2CHpyrrole), 122.78, 125.99, 128.99, 129.36, 129.81,