Efficient route for the synthesis of highly substituted pyrroles

Article abstract of DOI:10.1080/00397910903457266

A mild and efficient synthesis of highly substituted pyrroles using the reaction of triphenylphosphine, -diketone, ammonium acetate, and dialkyl acetylenedicarboxylates is described. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910903457266

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Efficient Route for the Synthesis of
Highly Substituted Pyrroles
Javad Azizian a , Javad Hosseini a , Mohammadkazem Mohammadi a
& Fatemeh Sheikholeslami a
a Department of Chemistry, Science and Research Branch, Islamic
Azad University, Tehran, Iran
Published online: 05 Nov 2010.
To cite this article: Javad Azizian , Javad Hosseini , Mohammadkazem Mohammadi & Fatemeh
Sheikholeslami (2010) Efficient Route for the Synthesis of Highly Substituted Pyrroles, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
40:23, 3472-3479, DOI: 10.1080/00397910903457266
To link to this article: http://dx.doi.org/10.1080/00397910903457266
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Synthetic Communications1, 40: 3472–3479, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903457266
EFFICIENT ROUTE FOR THE SYNTHESIS OF HIGHLY
SUBSTITUTED PYRROLES
Javad Azizian, Javad Hosseini, Mohammadkazem
Mohammadi, and Fatemeh Sheikholeslami
Department of Chemistry, Science and Research Branch, Islamic Azad
University, Tehran, Iran
A mild and efficient synthesis of highly substituted pyrroles using the reaction of triphenyl-
phosphine, a-diketone, ammonium acetate, and dialkyl acetylenedicarboxylates is
described.
Keywords: Dialkyl acetylenedicarboxylates; a-diketones; four-component synthesis; pyrroles;
triphenylphosphine
The pyrrole heterocycle is an important structural attribute in many bioactive
natural products,[1] therapeutic compounds,[2] and new organic materials,[3] and is
an intermediate in organic synthesis.[4] Consequently, the efficient assembly of this
class of molecule is a significant objective in synthetic chemistry. The construction
of the pyrrole ring system typically involves a multistep approach from preformed
intermediates, such as the classic Paal–Knorr cyclization reaction of 1,4-dicarbonyl
compounds and amines.[5–13] More contemporary transition-metal-based strategies
include the addition of chromium carbenes to dipolarophiles,[14a] the copper(I)-
catalyzed cycloisomerization of alkynyl imines,[14b] and rhodium-catalyzed reactions,
either N-H insertions[14c] or the reaction of isonitriles and 1,3-diketones.[14d] How-
ever, an alternative and more direct strategy is the combination of multiple
reactants in a single flask to afford the pyrrole core.
Herein, we report an efficient, inexpensive, convenient, and mild synthetic
route to highly substituted pyrroles in moderate yields without use of any catalyst.
Initially, we carried out the reaction of triphenylphosphine (1), ammonium acetate
(2), dimethyl acetylenedicarboxylate (DMAD) (3), and benzil (4) in dry acetonitrile
at room temperature; the condensation product 7 was obtained in moderate yield
(Scheme 1).
In the 1H NMR spectrum, the two methoxy groups were observed at d 3.77 and
3.90 as two singlets, and the NH proton resonated at d 9.29, supporting infrared (IR)
absorption at 3294 cmꢀ1. The 13C signals for the two ester carbonyls were seen at d
Received August 6, 2009.
Address correspondence to Javad Azizian, Department of Chemistry, Science and Research
Branch, Islamic Azad University, Tehran, Iran. E-mail: j-azizian@cc.sbu.ac.ir
3472

SYNTHESIS OF HIGHLY SUBSTITUTED PYRROLES
3473
Scheme 1. The reaction of benzil with DMAD and ammonium acetate in the presence of triphenylphosphine.
164.7 and 165.2. The reaction was found to be general and efficient. Interestingly, it
was found that the other a-diketones gave stable, isolable products; the results are
summarized in Table 1.
Table 1. Reaction of a-diketones with DMAD and ammonium acetate in the presence of triphenylphosphine

3474
J. AZIZIAN ET AL.
Table 2. Reaction of a-diketones with DEAD and ammonium acetate in the presence of triphenylphosphine
Diethyl acetylenedicarboxylate (DEAD) also elicited the same reactivity
pattern, and the results are tabulated in Table 2.
Mechanistically, the reaction may involve the initial generation of a zwitter-
ionic intermediate from triphenylphosphine and DMAD, which receives a proton

SYNTHESIS OF HIGHLY SUBSTITUTED PYRROLES
3475
Scheme 2. Mechanism of the reaction of benzil with DMAD and ammonium acetate in the presence of
triphenylphosphine.
from ammonium action to yield an intermediate vinyltriphenylphosphonium
cation (4). The attack of the conjugate base of ammonium cation (2) on the
vinyltriphenylphosphonium cation leads to phosphorane intermediate 5. Subse-
quently, the addition of the nitrogen atom of the intermediate 5 to the carbonyl
of a-diketone and the intramolecular Wittig reaction leads to heterocyclic system
6. In the final step this compound involves the proton-transfer reaction to afford
of aromatic heterocyclic system, as illustrated in Scheme 2.
In conclusion, the procedure that we have described here may be acceptable
for the preparation of highly functionalized pyrrole derivatives, which may be
considered for their known properties and as reactants for other syntheses.
EXPERIMENTAL
Dialkyl acetylenedicarboxylate, ammonium acetate, triphenylphosphine, and
a-diketone were obtained from Merck and Fluka (Buchs, Switzerland) and were used
without further purification. Melting points were measured on an Electrothermal 9100
apparatus and are uncorrected. Elemental analyses were performed using a Heraeus
1
CHN-O-Rapid analyzer. H and 13C NMR spectra were measured with a Bruker
DRX-300 Avance spectrometer at 300 and 75 MHz, respectively. Infrared (IR) spectra
were recorded on a Perkin-Elmer Fourier transform (FT)–IR spectrometer RX 1.
General Procedure for Synthesis of Highly Substituted-1H-pyrrole-
2,3-dicarboxlates
To a magnetically stirred solution of triphenylphosphine (0.524 g, 2 mmol) and
ammonium acetate (0.154 g, 2 mmol) in CH3CN (5 ml), a mixture of dialkyl acetyle-
nedicarboxylate (2 mmol) in CH3CN (5 ml) was added dropwise at ꢀ10 ꢁC over
10 min. The mixture was allowed to warm up to room temperature, and a-diketone
(2 mmol) was added and stirred for 22–24 h. The solvent was removed under reduced
pressure, and the viscous residue was purified by silica-gel (Merck silica gel 60,

3476
J. AZIZIAN ET AL.
230–400) column chromatography using ethyl acetate–hexane. The product was
obtained from recrystallization in ether.
Selected Data
Dimethyl 4,5-diphenyl-1H-pyrrole-2,3-dicarboxylate (7). Colorless crys-
tal, mp 185–186 ꢁC; IR (KBr) (vmax, cmꢀ1): 1687, 1731 (C O), 3294 (NH); 1H
=
NMR (300 MHz, CDCl3) dH 3.77, 3.90 (6H, 2s, OCH3), 7.28 (10H, m, arom), 9.29
(1H, bs, NH); 13C NMR (75 MHz, CDCl3) dC 52.5 and 52.7 (2OCH3), 120.2,
123.3, 123.6, 127.5, 128.2, 128.6, 128.7, 129.1, 130.1, 131.1, 133.3, 133.6 (arom),
=
160.9 and 166.6 (C O). Anal. calcd. for C20H17NO4: C, 71.36; H, 5.11; N, 4.18;
O, 19.08. Found: C, 71.12; H, 4.91; N, 3.89; O, 18.88.
Diethyl 4,5-diphenyl-1H-pyrrole-2,3-dicarboxylate (8). Colorless crystal,
mp 114–115 ꢁC; IR (KBr) (vmax, cmꢀ1): 1681, 1729 (C O), 3282 (NH); H NMR
1
=
3
(300 MHz, CDCl3) dH 1.19, 1.35 (6H, 2t, JHH ¼ 7.2 Hz, 2CH3), 4.23, 4.34 (4H,
3
2q, JHH ¼ 7.2 Hz, 2OCH2), 7.55 (10H, m, arom), 9.46 (1H, bs, NH); 13C NMR
(75 MHz, CDCl3) dC 14.3 and 14.6 (2CH3), 61.4 and 61.6 (2OCH2), 120.4, 123.4,
123.6, 127.4, 128.1, 128.5, 128.6, 129.1, 130.2, 131.2, 133.2, 133.8 (arom), 160.7
=
and 166.2 (C O). Anal. calcd. for C22H21NO4: C, 72.71; H, 5.82; N, 3.85; O,
17.61. Found: C, 72.32; H, 5.41; N, 3.19; O, 17.34.
Dimethyl 7H-acenaphtho[1,2-b]pyrrole-8,9-dicarboxylate (7a). Limonen
crystal, mp 226–228 ꢁC; IR (KBr) (vmax, cmꢀ1): 1686, 1725 (C O), 3264 (NH); H
1
=
NMR (300 MHz, CD3COCD3) dH 3.89, 3.99 (6H, 2s, OCH3), 7.61 (2H, m, arom),
7.87 (3H, m, arom), 8.01 (1H, d, arom), 12.10 (1H, bs, NH); 13C NMR (75 MHz,
CD3COCD3) dC 51.3 and 51.4 (2OCH3), 115.4, 120.9, 123.2, 126.5, 127.6, 127.8,
=
128.1, 128.4, 130,2, 132.2, 134.2 (arom), 160.5 and 164.5 (C O). Anal. calcd. for
C18H13NO4: C, 70.36; H, 4.26; N, 4.56; O, 20.83. Found: C, 70.12; H, 4.01; N,
4.19; O, 20.23.
Diethyl 7H-acenaphtho[1,2-b]pyrrole-8,9-dicarboxylate (8a). Limonen
crystal, mp 184–185 ꢁC; IR (KBr) (vmax, cmꢀ1): 1670, 1720 (C O), 3260 (NH); H
1
=
3
NMR (300 MHz, CD3COCD3) dH 1.37, 1.46 (6H, 2t, JHH ¼ 7.1 Hz, 2CH3), 4.36,
3
4.74 (4H, 2q, JHH ¼ 7.1 Hz, 2OCH2), 7.62 (2H, m, arom), 7.85 (3H, m, arom),
8.02 (1H, d, arom), 12.04 (1H, bs, NH); 13C NMR (75 MHz, CD3COCD3) dC 14.1
and 14.2 (2CH3), 60.6 and 60.7 (2OCH2), 115.3, 120.8, 123.1, 126.1, 126.4, 127.5,
=
127.8, 128.2, 128.3, 130.2 132.3, 134.1 (arom), 160.3 and 164.2 (C O). Anal. calcd.
for C20H17NO4: C, 71.63; H, 5.11; N, 4.18; O, 19.08. Found: C, 71.23; H, 3.99; N,
4.01; O, 18.91.
Dimethyl 1H-dibenzo[e,g]indole-2,3-dicarboxylate (7b). Red crystal, mp
256–257 ꢁC; IR (KBr) (vmax, cmꢀ1): 1687, 1729 (C O), 3317 (NH); 1H NMR
=
(300 MHz, CD3COCD3) dH 3.99 and 4.06 (6H, 2s, 2OCH3), 6.63 (2H, m, arom),
7.71 (2H, m, arom), 8.18 (1H, m, arom), 8.71 (1H, m, arom), 8.84 (2H, m, arom),
12.04 (1H, bs, NH); 13C NMR (75 MHz, CD3COCD3) dC 51.9 and 52.4 (2OCH3),
117.8, 117.9, 122.5, 123.0, 123.7, 124.2, 125.8, 127.3, 127.7, 127.8, 128.4, 130.2,
=
131.3 (arom), 160.6 and 168.0 (C O). Anal. calcd. for C20H15NO4: C, 72.06; H,
4.54; N, 4.20; O, 19.20. Found: C, 71.85; H, 4.11; N, 4.23; O, 19.03.

SYNTHESIS OF HIGHLY SUBSTITUTED PYRROLES
3477
Diethyl 1H-dibenzo[e,g]indole-2,3-dicarboxylate (8b). Red crystal, mp
221–223 ꢁC; IR (KBr) (vmax, cmꢀ1): 1683, 1725 (C O), 3315 (NH); 1H NMR
=
3
(300 MHz, CD3COCD3) dH 1.36 and 1.42 (6H, 2t, JHH ¼ 7.1 Hz, 2CH3), 4.33 and
3
4.54 (4H, 2q, JHH ¼ 7.1 Hz, 2OCH2), 6.65 (2H, m, arom), 7.41 (2H, m, arom),
7.98 (1H, m, arom), 8.61 (1H, m, arom), 8.74 (2H, m, arom), 12.10 (1H, bs, NH);
13C NMR (75 MHz, CD3COCD3) dC 14.1 and 14.2 (2CH3), 59.9 and 60.3
(2OCH2), 117.8, 117.9, 122.5, 123.0, 123.7, 124.2, 125.8, 127.3, 127.7, 127.8, 128.4,
=
130.2, 131.3 (arom), 160.6 and 168.0 (C O). Anal. calcd. for C20H15NO4: C,
72.06; H, 4.54; N, 4.20; O, 19.20. Found: C, 71.85; H, 4.11; N, 4.23; O, 19.03.
Dimethyl 5,4-dimethyl-1H-pyrrole-2,3-dicarboxylate (7d). Colorless crys-
tal, mp 116–117 ꢁC; IR (KBr) (vmax, cmꢀ1): 1656, 1778 (C O), 3280 (NH); H NMR
1
=
(300 MHz, CDCl3) dH 2.07 (3H, s, CH3), 2.21 (3H, s, CH3), 3.84 and 3.88 (6H, 2s,
OCH3), 9.25 (1H, bs, NH); 13C NMR (75 MHz, CDCl3) dC 10.1 (CH3), 11.4
(CH3), 52.1 and 52.1 (2OCH3), 118.8, 119.0, 121.4, 130.1 (arom), 161.1 and 166.6
=
(C O). Anal. calcd. for C10H13NO4: C, 56.87; H, 6.20; N, 6.63; O, 30.30. Found:
C, 56.47; H, 6.01; N, 6.23; O, 30.10.
Dimethyl 4,5-bis(4-chlorophenyl)-1H-pyrrole-2,3-dicarboxylate (7c). Col-
orless crystal, mp 190–191 ꢁC; IR (KBr) (vmax, cmꢀ1): 1686, 1737 (C O), 3278
=
1
(NH); H NMR (300 MHz, CDCl3) dH 3.77, 3.86 (6H, 2s, OCH3), 7.23 (8H, m,
arom), 9.69 (1H, bs, NH); 13C NMR (75 MHz, CDCl3) dC 52.6 and 52.7
(2OCH3), 120.8, 122.6, 123.1, 129.1, 129.2, 129.4, 129.5, 131.5, 131.9, 132.3, 133.8,
=
134.9 (arom), 160.9 and 166.6 (C O). Anal. calcd. for C20H15Cl2NO4: C, 59.42;
H, 3.74; N, 3.46; O, 15.83. Found: C, 59.32; H, 3.35; N, 3.30; O, 15.50.
Diethyl 4,5-bis(4-chlorophenyl)-1H-pyrrole-2,3-dicarboxylate (8c). Color-
less crystal, mp 165–166 ꢁC; IR (KBr) (vmax, cmꢀ1): 1677,1728 (C O), 3280 (NH);
=
3
1H NMR (300 MHz, CDCl3) dH 1.23, 1.37 (6H, 2t, JHH ¼ 7.2 Hz, 2CH3), 4.24,
3
4.36 (4H, 2q, JHH ¼ 7.2 OCH2), 7.27 (8H, m, arom), 9.29 (1H, bs, NH); 13C
NMR (75 MHz, CDCl3) dC 14.1 and 14.6 (2CH3), 61.6 and 61.7 (2OCH2), 120.4,
122.3, 123.1, 129.0, 129.3, 129.5, 129.5, 131.5, 131.9, 132.3, 133.7, 134.9 (arom),
=
161.1 and 166.7 (C O). Anal. calcd. for C22H19Cl2NO4: C, 61.12; H, 4.43; N,
3.24; O, 14.80. Found: C, 61.01; H, 4.13; N, 3.02; O, 14.40.
Diethyl 5,4-dimethyl-1H-pyrrole-2,3-dicarboxylate (8d). Colorless crystal,
mp 90–91 ꢁC; IR (KBr) (vmax, cmꢀ1): 1685, 1755 (C O), 3258 (NH); H NMR
1
=
3
(300 MHz, CDCl3) dH 1.26 and 1.31 (6H, 2t, JHH ¼ 7.2 Hz, CH3), 2.12 (3H, s,
CH3), 2.31 (3H, s, CH3), 4.26 and 4.31 (4H, 2q, OCH2), 9.23 (1H, bs, NH); 13C
NMR (75 MHz, CDCl3) dC 10.3 (CH3), 11.6 (CH3), 13.9 and 14.2 (2CH3), 59.9
=
and 60.1 (2OCH2), 119.1, 119.2, 121.6, 130.1 (arom), 161.2 and 166.5 (C O). Anal.
calcd. for C12H17NO4: C, 60.24; H, 7.16; N, 5.85; O, 26.75. Found: C, 60.17; H, 6.91;
N, 5.53; O, 26.40.
Dimethyl 5-ethyl-4-methyl-1H-pyrrole-2,3-dicarboxylate (7e). Colorless
crystal, mp 120–121 ꢁC; IR (KBr) (vmax, cmꢀ1): 1687, 1718 (C O), 3257 (NH); H
1
=
3
NMR (300 MHz, CDCl3) dH 1.08 (3H, t, JHH ¼ 7.2 Hz, CH3), 2.22 (3H, s, CH3),
3
2.50 (2H, q, JHH ¼ 7.2 Hz, CH2), 3.83 and 3.88 (6H, 2s, 2OCH3), 9.61 (1H, bs,
NH); 13C NMR (75 MHz, CDCl3) dC 11.2 (CH3), 15.9 (CH3), 18.35 (CH2), 50.1

3478
J. AZIZIAN ET AL.
=
and 50.2 (2OCH3), 118.7, 121.1, 125.2, 130.1 (arom), 160.9 and 166.2 (C O). Anal.
calcd. for C11H15NO4: C, 58.66; H, 6.71; N, 6.22; O, 28.41. Found: C, 58.35; H, 6.35;
N, 6.08; O, 28.32.
Diethyl 5-ethyl-4-methyl-1H-pyrrole-2,3-dicarboxylate (8e). Colorless
crystal, mp 79–82 ꢁC; IR (KBr) (vmax, cmꢀ1): 1677, 1724 (C O), 3295 (NH); H
1
=
3
NMR (300 MHz, CDCl3) dH 1.08 (3H, t, JHH ¼ 7.2 Hz, CH3), 1.31 and 1.36 (6H,
3
3
2t, JHH ¼ 7.1 Hz, 2CH3), 2.21 (3H, s, CH3), 2.48 (2H, q, JHH ¼ 7.2 Hz, CH2),
4.29, 4.34 (4H, 2q, JHH ¼ 7.1 Hz, 2OCH3), 9.61 (1H, bs, NH); 13C NMR
3
(75 MHz, CDCl3) dC 11.2 (CH3), 13.9, 14.6 (2CH3), 15.9 (CH3), 18.3 (CH2), 60.9
=
and 61.1 (2OCH2), 118.9, 121.5, 124.8, 129.9 (arom) 161.0 and 166.6 (C O). Anal.
calcd. for C13H19NO4: C, 61.64; H, 7.56; N, 5.53; O, 25.27. Found: C, 61.14; H, 7.15;
N, 5.13; O, 25.02.
Dimethyl 4,5-bis(4-methylphenyl)-1H-pyrrole-2,3-dicarboxylate (7f). Col-
orless crystal, mp 152–155 ꢁC; IR (KBr) (vmax, cmꢀ1): 1687, 1727 (C O), 3273 (NH);
=
1H NMR (300 MHz, CDCl3) dH 2.29, 2.38 (6H, 2 s, 2CH3), 3.67, 3.87 (6H, 2s,
OCH3), 7.25 (8H, m, arom), 9.67 (1H, bs, NH); 13C NMR (75 MHz, CDCl3) dC
14.2 and 21.1 (2CH3), 51.6 and 51.7 (2OCH3), 119.8, 122.9, 123.4, 128.4, 128.9,
=
129.1, 129.5, 131.5, 132.8, 133.1, 134.8, 135.2 (arom), 160.9 and 166.6 (C O). Anal.
calcd. for C22H21NO4: C, 72.72; H, 5.82; N, 3.85; O, 17.61. Found: C, 72.62; H, 5.45;
N, 3.30; O, 17.50.
Diethyl 4,5-bis(4-methylphenyl)-1H-pyrrole-2,3-dicarboxylate (8f). Color-
less crystal, mp 105–106 ꢁC; IR (KBr) (vmax, cmꢀ1): 1672, 1729 (C O), 3279 (NH);
=
3
1H NMR (300 MHz, CDCl3) dH 1.21, 1.37 (6H, 2t, JHH ¼ 7.2 Hz, 2CH3), 2.29,
3
2.37 (6H, 2s, 2CH3), 4.21, 4.37 (4H, 2q, JHH ¼ 7.2 OCH2), 7.27 (8H, m, arom),
9.29 (1H, bs, NH); 13C NMR (75 MHz, CDCl3) dC 14.1,14.2, 14.6, 21.7 (4CH3),
61.5 and 61.8 (2OCH2), 120.2, 122.3, 123.4, 128.2, 128.4, 129.1, 129.5, 131.5,
=
131.9, 132.3, 133.7, 134.9 (arom), 161.2 and 166.7 (C O). Anal. calcd. for
C24H25NO4: C, 73.62; H, 6.64; N, 3.58; O, 16.35. Found: C, 73.31; H, 6.43; N,
3.42; O, 16.20.
REFERENCES
1. (a) Lindquist, N.; Fenical, W.; Van Duyne, G. D.; Clardy, J. New alkaloids of the
lamellarin class from the marine ascidian Didemnum chartaceum (Sluiter, 1909). J. Org.
Chem. 1988, 53, 4570–4574.
2. (a) Colotta, V.; Cecchi, L.; Melani, F.; Filacchioni, G.; Martini, C.; Giannaccini, G.;
Lucacchini, A. Tricyclic heteroaromatic systems: [1]Benzopyranopyrrol-4-ones and
[1]benzopyrano-1,2,3-triazol-4-ones as benzodiazepine receptor ligands: Synthesis and
structure-activity relationships. J. Med. Chem. 1990, 33, 2646–2651; (b) Cozzi, P.;
Mongelli, N. Cytotoxics derived from distamycin A and congeners. Curr. Pharm. Des.
1998, 4, 181–201.
3. (a) Curran, D.; Grimshaw, J.; Perera, S. D. Poly (pyrrole) as a support for electrocatalytic
materials. Chem. Soc. Rev. 1991, 20, 391–404; (b) Lee, C. F.; Yang, L. M.; Hwu, T. Y.;
Feng, A. S.; Tseng, J. C.; Luh, T. Y. One-pot synthesis of substituted furans and
pyrroles from propargylic dithioacetals: New annulation route to highly photoluminescent
oligoaryls. J. Am. Chem. Soc. 2000, 122, 4992–4993 and references therein.

SYNTHESIS OF HIGHLY SUBSTITUTED PYRROLES
3479
4. Boger, D. L.; Boyce, C. W.; Labrilli, M. A.; Sehon, C. A.; Jin, Q. Total syntheses of
ningalin A, lamellarin O, lukianol A, and permethyl storniamide A utilizing heterocyclic
azadiene Diels–Alder reactions. J. Am. Chem. Soc. 1999, 121, 54.
5. Nair, V.; Vinod, A. U.; Rajesh, C. A novel synthesis of 2-aminopyrroles using a
three-component reaction. J. Org. Chem. 2001, 66, 4427.
6. Bharadwaj, A. R.; Scheidt, K. A. Catalytic multicomponent synthesis of highly
substituted pyrroles utilizing a one-pot Sila–Stetter=Paal–Knorr strategy. Org. Lett.
2004, 6, 2465.
7. Tejedor, D.; Gonzalez-Cruz, D.; Garcia-Tellado, F. A diversity-oriented strategy for the
construction of tetrasubstituted pyrroles via coupled domino processes. J. Am. Chem. Soc.
2004, 126, 8390.
8. Azizian, J.; Karimi, A.; Arefrad, H. A novel one-pot, four-component synthesis of some
densely functionalized pyrroles. Mol. Divers. 2003, 223–226.
9. Lee, H. S.; Kim, J. M.; Kim, J. N. Synthesis of poly-substituted pyrroles starting from the
Baylis–Hillman adducts. Tetrahedron Lett. 2007, 48, 4119–4122.
10. Azizian, J.; Mohammadi, A.; Karimi, A. An efficient one-pot procedure for preparation
of 2,4(1H,3H)-quinazolinediones and 2-thioxoquinazolinone derivatives under microwave
irradiation. Synth. Commun. 2003, 33, 1532–2432.
11. Azizian, J.; Mehrdad, M.; Jadidi, K.; Sarrafi, Y. Rearrangement of 4-imino-(1H,4H)-3,1-
benzoxazine-2-ones to 2,4-quinazolinediones via an isocyanate carboxamide intermediate.
Tetrahedron Lett. 2000, 41, 5265.
12. Yadav, J. S.; Subba Reddy, B. V.; Srinivasa Rao, T.; Narender, R.; Gupta, M. K. PMA=
SiO2 as efficient, cost-effective, and recyclable catalytic system for the synthesis of highly
substituted pyrroles. J. Mol. Catal. A: Chem. 2007, 278, 42–46.
13. Amarnath, V.; Anthony, D.; Amarnath, K.; Valentine, W. M.; Wetterau, L. A.; Graham,
D. G. Intermediates in the Paal–Knorr synthesis of pyrroles. J. Org. Chem. 1991, 56,
6924–6931.
14. (a) Merlic, C. A.; Baur, A.; Aldrich, C. C. Acylamino chromium carbene complexes:
Direct carbonyl insertion, formation of munchnones, and trapping with dipolarophiles.
¨
J. Am. Chem. Soc. 2000, 122, 7398–7399; (b) Kel’in, A. V.; Sromek, A. W.; Gevorgyan,
V. A novel Cu-assisted cycloisomerization of alkynyl Imines: Efficient synthesis of
pyrroles and pyrrole-containing heterocycles. J. Am. Chem. Soc. 2001, 123, 2074–2075;
(c) Wang, Y. L.; Zhu, S. Z. Convenient synthesis of polyfunctionalized b-fluoropyrroles
from rhodium(II)-catalyzed intramolecular NꢀH insertion reactions. Org. Lett. 2003, 5,
745–748; (d) Akaya, H.; Kojima, S.; Murahashi, S. I. Rhodium complex–catalyzed
reaction of isonitriles with carbonyl compounds: Catalytic synthesis of pyrroles. Org. Lett.
2001, 3, 421–424.