Novel one-pot, three-component synthesis of new 2-alkyl-5-aryl-(1H)- pyrrole-4-ol in water

Article abstract of DOI:10.1021/jo702385n

(Chemical Equation Presented) New 2-alkyl-5-aryl-(1H)-pyrrole-4-ol derivatives were synthesized via three-component reaction of β-dicarbonyl compounds with arylglyoxals in the presence of ammonium acetate in water at room temperature.

Full text of DOI:10.1021/jo702385n

Novel One-Pot, Three-Component Synthesis of New
2-Alkyl-5-aryl-(1H)-pyrrole-4-ol in Water
Behzad Khalili,† Pedram Jajarmi,‡ Bagher Eftekhari-Sis,† and Mohammed M. Hashemi*,†
Department of Chemistry, Sharif UniVersity of Technology, P.O. Box 11365-9516, Tehran, Iran, and
Department of Material Science and Engineering, Tarbiat Moallem UniVersity of SabzeVar, SabzeVar, Iran
mhashemi@sharif.ir
ReceiVed NoVember 4, 2007
New 2-alkyl-5-aryl-(1H)-pyrrole-4-ol derivatives were synthesized via three-component reaction of
â-dicarbonyl compounds with arylglyoxals in the presence of ammonium acetate in water at room
temperature.
Introduction
highly desirable in recent years to meet environmental consid-
erations.4 The use of water as a sole medium for organic
reactions would greatly contribute to the development of
environmentally friendly processes. Indeed, industry prefers to
use water as a solvent rather than toxic organic solvents.
Pyrroles are important heterocycles broadly used in material
science5 and found in naturally occurring and biologically
important molecules.6 Pyrroles can be found in a tremendous
range of natural products7 and bioactive molecules,8 including
the blockbuster drug, atrovastatin calcium,8a as well as important
anti-inflammatants,8b antitumoragents,8c andimmunosuppressants.8d
At the beginning of the new century, a shift in emphasis in
chemistry is apparent with the desire to develop environmentally
benign routes to a myriad of materials.1 Green chemistry
approaches hold out significant potential not only for reduction
of byproducts, a reduction in the waste produced, and lowering
of energy costs but also in the development of new methodolo-
gies toward previously unobtainable materials, using existing
technologies.2 Of all of the existing areas of chemistry, medicinal
and pharmaceutical chemistry, with their traditionally large
volume of waste/product ratio, are perhaps the most ripe for
greening.3
(4) (a) Grieco, P. A. Organic Synthesis in Water; Blackie Academic and
Professional: London, 1998. (b) Demko, Z. P.; Sharpless, K. B. J. Org.
Chem. 2001, 66, 7945. (c) Li, C.-J. Chem. Rev. 2005, 105, 3095.
(5) For a recent review on conjugated polymers incorporating the pyrrole
unit, see: (a) Higgins, S. Chem. Soc. ReV. 1997, 26, 247-257. For some
recent examples on the use of pyrrole derivatives in material science, see:
(b) Lee, C.-F.; Yang, L.-M.; Hwu, T.-Y.; Feng, A.-S.; Tseng, J.-C.; Luh,
T.-Y. J. Am. Chem. Soc. 2000, 122, 4992 and references therein. (c) Ogawa,
K.; Rasmussen, R. C. J. Org. Chem. 2003, 68, 2921-2928. (d) Naji, A.;
Cretin, M.; Persin, M.; Sarrazin, J. J. Membr. Sci. 2003, 212, 1-11. (e)
Chen, J.; Too, C. O.; Wallace, G. G.; Swiegers, G. F.; Skelton, B. W.;
White, A. H. Electrochim. Acta 2002, 47, 4227-4238. (f) Zotti, G.; Zecchin,
S.; Schiavon, G.; Berlin, A. Chem. Mater. 2002, 14, 3607-3614. (g) Glidle,
A.; Swann, M. J.; Hadyoon, C. S.; Cui, L.; Davis, J.; Ryder, K. S.; Cooper,
J. M. J. Electron. Spectrosc. 2001, 121, 131-148. (h) Pleus, S.; Schulte,
B. J. Solid State Electrochem. 2001, 5, 522-530. (i) Korri-Youssoufi, H.;
Makrouf, B.; Yassar, A. Mater. Sci. Eng., C 2001, 15, 265-268. (j) Gale,
P. A.; Bleasdale, E. R.; Chen, G. Z. Supramol. Chem. 2001, 13, 557- 563.
(k) Costello, B. P. J. D.; Evans, P.; Guernion, N.; Ratcliffe, N. M.; Sivanand,
P. S.; Teare, G. C. Synth. Met. 2001, 118, 199-200. (l) Chou, S. S. P.;
Yeh, Y. H. Tetrahedron Lett. 2001, 42, 1309-1311. (m) Tietze, L. F.;
Kettschau, G.; Heuschert, U.; Nordmann, G. Chem. Eur. J. 2001, 7, 368-
373.
The organic reactions in aqueous media have attracted much
attention in synthetic organic chemistry, not only because water
is one of the most abundant, cheap, and environmentally friendly
solvents but also because water exhibits unique reactivity and
selectivity, properties that are different from those of conven-
tional organic solvents. Thus, development of novel reactivity
as well as selectivity that cannot be attained in conventional
organic solvents is one of the challenging goals of aqueous
chemistry.1 Carrying out organic reactions in water has become
† Sharif University of Technology.
‡ Tarbiat Moallem University of Sabzevar.
(1) Anastas, P.; Williamson, T. Green Chemistry, Frontiers in Benign
Chemical Synthesis and Procedures; Oxford Science Publications: New
York, 1998.
(2) Cave, G. W. V.; Raston, C. L.; Scott, J. L. Chem. Commun. 2001,
2159-2169.
(3) As estimated by determination of E-factor: Sheldon, R. A. Chem.
Ind. 1997, 12.
10.1021/jo702385n CCC: $40.75 © 2008 American Chemical Society
Published on Web 02/22/2008
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J. Org. Chem. 2008, 73, 2090-2095

Synthesis of New 2-Alkyl-5-aryl-(1H)-pyrrole-4-ol
SCHEME 1. Retro Synthesis of 5-Aryl-(1H)-pyrrole-4-ol
Within these large classes of relevant products, tetrasubstituted
pyrroles are extremely important, displaying antibacterial,
antiviral, anticonvulsant, and antioxidant activities and inhibiting
cytokine-mediated diseases.9 Accordingly, substantial attention
has been paid to develop efficient methods for the synthesis of
pyrroles.5,6,10
One of the most common approaches to pyrrole synthesis is
the Paal-Knorr reaction in which 1,4-dicarbonyl compounds
are converted to pyrrole via acid-mediated dehydrative cycliza-
tion in the presence of a primary amine.11 In this reaction, the
1,4-dicarbonyl compounds provide the four carbons of the
pyrrole with the possible substituents, whereas the amine
provides the nitrogen with its substituent. The main limitations
to intensive use of this reaction are the strong reaction conditions
required for cyclization (use of boiling acetic acid for extended
times) and the low availability of nonsymmetrically substituted
1,4-dicarbonyl compounds. The classical approach to this class
of products is the condensation of enolates with phenacyl
bromides,12 thus limiting the preparation to pyrroles with aryl
substituents. Alternative approaches need several steps of
reactions with chromatographic separations to obtain the
intermediates for cyclization. Therefore, mild reaction conditions
that can overcome some of the shortcomings of previous
methods are necessary. In this contribution, we describe one-
pot synthesis of new 5-aryl-(1H)-pyrrole-4-ol 1 via reaction of
â-dicarbonyl compounds 3 with arylglyoxals 2 in the presence
of excess ammonium acetate (Scheme 1). To the best of our
knowledge, there are no reports in the literature for the formation
of 4-hydroxypyrrole derivatives via condensation of â-dicar-
bonyl compounds with arylglyoxals.
(6) (a) Trofimov, B. A.; Sobenina, L. N.; Demenev, A. P.; Mikhaleva,
A. I. Chem. ReV. 2004, 104, 2481-2506. (b) Black, D. S. 1H-Pyrrole. In
Science of Synthesis; Thieme: Stuttgart, 2001; Chapter 13, p 441. (c) Sayah,
B.; Pelloux-Leon, N.; Vallee, Y. J. Org. Chem. 2000, 65, 2824. (d) Liu,
J.-H.; Yang, Q.-C.; Mak, T. C. W.; Wong, H. N. C. J. Org. Chem. 2000,
65, 3587. (e) Boger, D. L.; Boyce, C. W.; Labroli, M. A.; Sehon, C. A.;
Jin, Q. J. Am. Chem. Soc. 1999, 121, 54. (f) Fu¨rstner, A.; Weintritt, H. J.
Am. Chem. Soc. 1998, 120, 2817. (g) Gossauer, A. Pyrrole. In Houben-
Weyl; Thieme: Stuttgart, 1994; E6a/1, p 556.
One-pot multicomponent processes have recently gained a
considerable and steadily increasing academic, economic, and
(10) For a review on recent advances in the synthesis of pyrroles, see:
(a) Ferreira, V. F.; de Souza, M. C. V. B.; Cunha, A. C.; Pereira, L. O. R.;
Ferreira, M. L. G. Org. Prep. Proced. Int. 2001, 33, 411-454. For a recent
review on synthesis of aromatic heterocycles, see: (b) Gilchrist, T. L. J.
Chem. Soc., Perkin Trans. 1 2001, 2491-2515. For some recent examples
on the synthesis of pyrrole derivatives, see: (c) Gilchrist, T. L. J. Chem.
Soc., Perkin Trans. 1 1999, 2849. (d) Tarasova, O. A.; Nedolya, N. A.;
Vvedensky, V. Yu.; Brandsma, L.; Trofimov, B. A. Tetrahedron Lett. 1997,
38, 7241. (e) Azizian, J.; Karimi, A. R.; Arefrad, H.; Mohammadi, A. A.;
Mohammadizadeh, M. R. Mol. DiVersity 2003, 6, 223-226. (f) Trofimov,
B. A.; Demenev, A P.; Sobenina, L. N.; Mikhaleva, A. I.; Tarasova, O. A.
Tetrahedron Lett. 2003, 44, 3501-3503. (g) Ranu, B. C.; Dey, S. S.
Tetrahedron Lett. 2003, 44, 2865-2868. (h) Zhang, X. Q.; Sui, Z.
Tetrahedron Lett. 2003, 44, 3071-3073. (i) Quiclet-Sire, B.; Quintero, L.;
Sanchez-Jimenez, G.; Zard, S. Z. Synlett 2003, 75-78. (j) Kim, J. T.; Kel’in,
A. V.; Gevorgyan, V. Angew. Chem., Int. Ed. 2003, 42, 98-101. (k) Okada,
H.; Akaki, T.; Oderaotoshi, Y.; Minakata, S.; Komatsu, M. Tetrahedron
2003, 59, 197-205. (l) Bullington, J. L.; Wolff, R. R.; Jackson, P. F. J.
Org. Chem. 2002, 67, 9439-9442. (m) Demir, A. S.; Akhmedov, D. M.;
Sesenoglu, O. Tetrahedron 2002, 58, 9793-9799. (n) Langer, P.; Freifeld,
I. Chem. Commun. 2002, 2268-2269. (o) Deng, G. S.; Jiang, N.; Ma, Z.
H.; Wang, J. B. Synlett 2002, 1913-1915. (p) Attanasi, O. A.; De
Crescentini, L.; Favi, G.; Filippone, P.; Mantellini, F.; Santeusanio, S. J.
Org. Chem. 2002, 67, 8178-8181. (q) Bergman, J.; Rehn, S. Tetrahedron
2002, 58, 9175-9185. (r) Smith, N. D.; Huang, D. H.; Cosford, N. D. P.
Org. Lett. 2002, 4, 3537-3539. (s) Balme, G. Angew. Chem., Int. Ed. 2004,
43, 6238-6241. (t) Palacios, F.; Aparico, D.; de los Santos, J. M.; Vicario,
J. Tetrahedron 2001, 57, 1961-1972.
(11) Some recent applications of the Paal-Knorr synthesis: (a) Dong,
Y.; Naranjan, N.; Ablaza, S. L.; Yu, S.-X.; Bolvig, S.; Forsyth, D. A.; Le
Quesne, P. W. J. Org. Chem. 1999, 64, 2657. (b) Haubmann, C.; Huebner,
H.; Gmeiner, P. Bioorg. Med. Chem. Lett. 1999, 9, 3143. (c) Robertson, J.;
Hatley, R. J. D.; Watkin, D. J. J. Chem. Soc., Perkin. Trans. 1 2000, 3389.
(d) Wurtz, N. R.; Turner, J. M.; Baird, E. E.; Dervan, P. B. Org. Lett 2001,
3, 1201. (e) Ballini, R.; Bosica, G.; Fiorini, G.; Giarlo, G. Synthesis 2001,
2003. (f) Braun, R. U.; Zeitler, K.; Mu¨ller, T. J. J. Org. Lett. 2001, 3, 3297.
(g) Arrowsmith, J.; Jennings, S. A.; Clark, A. S.; Stevens, M. F. G. J. Med.
Chem. 2002, 45, 5458. For other syntheses of pyrroles, see: (h) Bartolo,
G.; Salerno, G.; Fazio, A. J. Org. Chem. 2003, 68, 7853 and references
therein. (i) Braun, R. U.; Mu¨ller, T. J. J. Synthesis 2004, 2391-2406. (j)
Trost, B. M.; Doherty, G. A. J. Am. Chem. Soc. 2000, 122, 3801-3810.
(k) Tracey, M. R.; Hsung, R. P.; Lambeth, R. H. Synthesis 2004, 918-
922.
(7) Jones, R. A. Pyrroles, Part II; Wiley: New York, 1992.
(8) (a) Thompson, R. B. FASEB J. 2001, 15, 1671. (b) Muchowski, J.
M. AdV. Med. Chem. 1992, 1, 109. (c) Cozzi, P.; Mongelli, N. Curr. Pharm.
Des. 1998, 4, 181. (d) Fu¨rstner, Thompson, R. B. FASEB J. 2001, 15, 1671.
(e) Bird, C. W., Ed. ComprehensiVe Heterocyclic Chemistry; Pergamon
Press: Oxford, 1996; Vol. 2. For some recent examples on biological activity
of pyrrole derivatives, see: (f) Micheli, F.; Di Fabio, R.; Cavanni, P.;
Rimland, J. M.; Capelli, A. M.; Chiamulera, C.; Corsi, M.; Corti, C.; Donati,
D.; Feriani, A.; Ferraguti, F.; Maffeis, M.; Missio, A.; Ratti, E.; Paio, A.;
Pachera, R.; Quartaroli, M.; Reggiani, A.; Sabbatini, F. M.; Trist, D. G.;
Ugolini, A.; Vitulli, G. Bioorg. Med. Chem. 2003, 11, 171-183. (g) Mach,
R. H.; Huang, Y. S.; Freeman, R. A.; Wu, L.; Blair, S.; Luedtke, R. R.
Bioorg. Med. Chem. 2003, 11, 225-233. (h) Bleicher, K. H.; Wuthrich,
Y.; Adam, G.; Hoffmann, T.; Sleight, A. J. Bioorg. Med. Chem. Lett. 2002,
12, 3073-3076. (i) Hackling, A. E.; Stark, H. ChemBioChem 2002, 3, 946-
961. (j) El-Gaby, M. S. A.; Gaber, A. M.; Atalla, A. A.; Al-Wahab, K. A.
A. Farmaco 2002, 57, 613-617. (k) Silvestri, R.; De Martino, G.; Artico,
M.; La Regina, G.; Ragno, R.; Loddo, R.; La Colla, P.; Marongiu, M. E.;
La Colla, M.; Pani, A. Med. Chem. Res. 2002, 11, 195-218. (l) Yanagimoto,
K.; Lee, K. G.; Ochi, H.; Shibamoto, T. J. Agric. Food Chem. 2002, 50,
5480-5484. (m) Bergauer, M.; Hubner, H.; Gmeiner, P. Bioorg. Med. Chem.
Lett. 2002, 12, 1937-1940. (n) Di Santo, R.; Costi, R.; Artico, M.; Ragno,
R.; Massa, S.; La Colla, M.; Loddo, R.; La Colla, P.; Pani, A. Med. Chem.
Res. 2002, 11, 153-167. (o) Borthwick, A. D.; Crame, A. J.; Ertl, P. F.;
Exall, A. M.; Haley, T. M.; Hart, G. J.; Mason, A. M.; Pennell, A. M. K.;
Singh, O. M. P.; Weingarten, G. G.; Woolven, J. M. J. Med. Chem. 2002,
45, 1-18. (p) Sessler, J. L.; Kral, V.; Shishkanova, T. V.; Gale, P. A. Proc.
Natl. Acad. Sci. U.S.A. 2002, 99, 4848-4853. (q) Lee, H.; Lee, J.; Lee, S.;
Shin, Y.; Jung, W. H.; Kim, J. H.; Park, K.; Kim, K.; Cho, H. S.; Ro, S.;
Lee, S.; Jeong, S.; Choi, T.; Chung, H. H.; Koh, J. S. Bioorg. Med. Chem.
Lett. 2001, 11, 3069-3072. (r) Andreani, A.; Cavalli, A.; Granaiola, M.;
Guardigli, M.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.;
Recanatini, M.; Roda, A. J. Med. Chem. 2001, 44, 4011-4014. (s) Brower,
J. O.; Lightner, D. A.; McDonagh, A. F. Tetrahedron 2001, 57, 7813-
7828. (t) Furstner, A.; Grabowski, E. J. ChemBioChem 2001, 2, 706-709.
(u) Seki, M.; Mori, K. Eur. J. Org. Chem. 2001, 503-506. (v) White, C.
M.; Satz, A. L.; Bruice, T. C.; Beerman, T. A. Proc. Natl. Acad. Sci. U.S.A.
2001, 98, 10590-10595. (w) Hidalgo, F. J.; Alaiz, M.; Zamora, R. Chem.
Res. Toxicol. 2001, 14, 582-588.
(9) (a) Kaiser, D. G.; Glenn, E. M. J. Pharm. Sci. 1972, 61, 1908. (b)
Daisone, G.; Maggio, B.; Schillaci, D. Pharmazie 1990, 45, 441. (c)
Almerico, A. M.; Diana, P.; Barraja, P.; Dattolo, G.; Mingoia, F.; Putzolu,
M.; Perra, G.; Milia, C.; Musiu, C.; Marongiu, M. E. Farmaco 1997, 52,
667. (d) Lehuede, J.; Fauconneau, B.; Barrier, L.; Ourakow, M.; Piriou,
A.; Vierfond, J. M. Eur. J. Med. Chem. 1999, 34, 991. (e) Chong, P. H.;
Bachenheimer, B. S. Drugs 2000, 11, 351. (f) Pinna, G. A.; Loriga, G.;
Murineddu, G.; Grella, G.; Mura, M.; Vargiu, L.; Murgioni, C.; La Colla,
P. Chem. Pharm. Bull. 2001, 49, 1406. (g) Iwao, M.; Takeuchi, T.; Fujikawa,
N.; Fukuda, T.; Ishibashi, F. Tetrahedron Lett. 2003, 44, 4443.
(12) See for example: Pinna, G. A.; Curzu, M. M.; Sechi, M.; Chelucci,
G.; Maciocco, E. Farmaco 1999, 54, 542.
(13) (a) Ugi, I.; Do¨mling, A.; Werner, B. J. Heterocycl. Chem. 2000,
37, 647. (b) Posner, G. H. Chem. ReV. 1986, 86, 831. (c) Weber, L.; Illgen,
K.; Almstetter, M. Synlett 1999, 366.
(14) Kobayashi, S. Chem. Soc. ReV. 1999, 28, 1.
(15) Riley, H. A.; Gray, A. R. Organic Syntheses; Wiley & Sons: New
York, NY, 1943; Collect. Vol. II, p 509.
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Khalili et al.
SCHEME 2. Synthesis of Arylglyoxals
The proposed mechanism involves the attack of enolate 52
onto the phenylglyoxal 5 as shown in Scheme 4, then in situ
generated 3-hydroxy-1,4-dicarbonyl compound 53, in the pres-
ence of NH4+, converts to 54, which then loses two H2O
molecules to afford products 21.
In the case of dicarbonyl compounds 16-18, in which R )
Ph, dicarbonyl compounds were recovered without any changes,
and unexpected 4(5)-aryl-2-aryloyl-(1H)-imidazol (55) was
obtained as a sole product (Scheme 5). Imidazol 55 was obtained
in two isomeric forms; 2-benzoyl-4-phenyl-(1H)-imidazol and
2-benzoyl-5-phenyl-(1H)-imidazol.
In conclusion, we have demonstrated a novel arylglyoxal-
mediated synthesis of new 4-hydroxy pyrroles from â-dicarbonyl
compounds and ammonium acetate in water. Considering the
availability of the starting materials, the simple procedure at
room temperature, and the robust nature of this chemical process,
this provides a very straightforward route to construct variously
substituted 4-hydroxy pyrroles without metal catalysts. Studies
directed toward the further generalization of this approach, as
well as the application of this method to other heterocycles,
are underway.
SCHEME 3. Synthesis of 5-Aryl-(1H)-pyrrole-4-ol
Experimental Section
ecological interest because they address very fundamental
principles of synthetic efficiency and reaction design.13 Ad-
ditionally, the prospect of extending one-pot reactions into
combinatorial and solid-phase syntheses13c,14 promises manifold
opportunities for developing novel lead structures of pharma-
ceuticals, catalysts, and even novel molecule-based materials.
Sample Procedures for Pyrrole Synthesis. To a mixture of
â-dicarbonyl compound (1 mmol) in water (5 mL), were succes-
sively added arylglyoxal (1 mmol) and ammonium acetate (5 mmol)
at room temperature (20-25 °C); the resultant mixture was stirred
at the same temperature for 30-45 min. After an appropriate time
the reaction mixture was solidified; the obtained solid was then
filtered, the filtrate washed with water (3 × 10 mL), and the crude
material was purified by crystallization from ethanol.
Results and Discussion
3-Acetyl-4-hydroxy-2-methyl-5-phenyl-1H-pyrrol (19): a yel-
low solid, mp: decomposed at 236 °C. 1H NMR (500 MHz, DMSO-
d6): δ 10.52 (s, 1H, NH), 9.50 (s, 1H, OH), 7.16 (d, J ) 7.7 Hz,
2H), 6.76 (t, J ) 7.7 Hz, 2H), 6.51 (t, J ) 7.35 Hz, 1H), 2.01 (s,
3H), 1.86 (s, 3H). 13C NMR (125 MHz, DMSO-d6): δ 197.5, 145.2,
132.6, 131.8, 128.6, 124.2, 123.0, 111.3, 110.1, 23.7, 14.7. IR (KBr,
cm-1): 3250, 3130, 3050, 1638, 1562, 1476, 1394, 1216, 1083,
766, 713, 582. Anal. Calcd for C13H13NO2: C, 72.54; H, 6.09; N,
6.51. Found: C, 72.51; H, 6.10; N, 6.52.
The arylglyoxals 2 were prepared from commercially avail-
able acetophenones 4 as outlined in Scheme 2.15 Twenty-eight
examples of the conversion arylglyoxals 2 to various tetrasub-
stituted pyrroles systems are listed in Table 1. The reactions
were performed by adding arylglyoxals 2 to mixtures of the
â-dicarbonyl compounds 3 in water at room-temperature in the
presence of excess amounts of NH4OAc at room-temperature
(Scheme 3). After 10-30 min, the mixture was solidified and
isolated by filtering. The products were obtained in good yields
after recrystallization in ethanol (96%).
Methyl 4-Hydroxy-2-methyl-5-phenyl-1H-pyrrole-3-carboxy-
late (20): a white solid, mp: decomposed at 233 °C. 1H NMR (500
SCHEME 4. Plausible Mechanism for Reaction of Ethyl Acetoacetate with Phenylglyoxal in the Presence of NH4OAc
SCHEME 5
2092 J. Org. Chem., Vol. 73, No. 6, 2008

Synthesis of New 2-Alkyl-5-aryl-(1H)-pyrrole-4-ol
TABLE 1. Synthesis of 5-Aryl-(1H)-pyrrole-4-ol
J. Org. Chem, Vol. 73, No. 6, 2008 2093

Khalili et al.
MHz, DMSO-d6): δ 10.55 (s, 1H, NH), 7.76 (m, 2H), 7.28 (m,
3H), 2.35 (s, 3H). 13C NMR (125 MHz, DMSO-d6): δ 166.3, 145.3,
133.5, 132.8, 127.6, 126.2, 122.9, 112.5, 111.9, 60.3, 18.1. IR (KBr,
cm-1): 3209, 3060, 2947, 2883, 1713, 1659, 1538, 1444, 1342,
1194, 1038, 736, 643. Anal. Calcd for C13H13NO3: C, 67.52; H,
5.67; N, 6.06. Found: C, 67.46; H, 5.65; N, 6.16.
Ethyl 4-Hydroxy-2-methyl-5-phenyl-1H-pyrrole-3-carboxy-
late (21): a white solid, mp: decomposed at 232 °C. 1H NMR (500
MHz, DMSO-d6): δ 10.54 (s, 1H, NH), 7.62 (d, J ) 7.5 Hz, 2H),
7.38 (t, J ) 7.45 Hz, 2H), 7.15 (t, J ) 7.40 Hz, 1H), 3.92 (q, J )
7.10 Hz, 2H), 2.50 (s, 3H), 1.42 (t, J ) 7.15 Hz, 3H). 13C NMR
(125 MHz, DMSO-d6): δ 164.2, 145.8, 133.0, 132.3, 128.9, 124.8,
123.9, 112.0, 110.9, 59.1, 17.8, 16.3. IR (KBr, cm-1): 3230, 3068,
2981, 1690, 1660, 1518, 1443, 1333, 1182, 1079, 1036, 735. Anal.
Calcd for C14H15NO3: C, 68.56; H, 6.16; N, 5.71. Found: C, 68.47;
H, 6.12; N, 5.65.
tert-Butyl-4-hydroxy-2-methyl-5-phenyl-1H-pyrrole-3-car-
boxylate (22): a white solid, mp: decomposed at 237 °C. 1H NMR
(500 MHz, DMSO-d6): δ 10.41 (s, 1H, NH), 7.77 (d, J ) 5.35
Hz, 2H), 7.28 (m, 3H), 2.31 (s, 3H), 1.29 (s, 9H). 13C NMR (125
MHz, DMSO-d6): δ 169.8, 145.8, 133.0, 132.3, 128.9, 124.8, 123.9,
112.0, 110.9, 79.8, 27.8, 14.44. IR (KBr, cm-1): 3241, 3065, 2981,
2931, 1717, 1687, 1666, 1521, 1345, 1165, 1001, 729. Anal. Calcd
for C16H19NO3: C, 70.31; H, 7.01; N, 5.12. Found: C, 70.29; H,
7.00; N, 5.08.
3213, 3076, 2980, 2931, 1708, 1643, 1547, 1518, 1454, 1386,
1245, 1156, 1120, 1076, 999, 842, 762, 605. Anal. Calcd for C16H18-
FNO3: C, 65.97; H, 6.23; N, 4.81. Found: C, 66.0; H, 6.11; N,
5.01.
Ethyl 5-(4-Fluorophenyl)-4-hydroxy-2-propyl-1H-pyrrole-3-
carboxylate (31): a pale-yellow solid, mp: decomposed at
1
234 °C. H NMR (500 MHz, DMSO-d6): δ 10.52 (s, 1H, NH),
7.78 (m, 2H), 7.16 (m, 2H), 3.95 (m, 2H), 2.73 (m, 2H), 1.49 (m,
1H), 1.38 (m, 1H), 1.11 (t, J ) 7.05 Hz, 3H), 0.81 (t, J ) 7.2 Hz,
3H). 13C NMR (125 MHz, DMSO-d6): δ 165.9, 160.7, 131.8, 130.9,
126.8, 119.1, 116.0, 112.8, 112.0, 56.1, 30.2, 24.1, 16.1, 14.7. IR
(KBr, cm-1): 3245, 3072, 2980, 1699, 1647, 1506, 1462, 1345,
1241, 1176, 1031, 842, 782, 681. Anal. Calcd for C16H18FNO3:
C, 65.97; H, 6.23; N, 4.81. Found: C, 66.0; H, 6.37; N, 4.80.
Methyl 4-Hydroxy-5-(4-methoxyphenyl)-2-methyl-1H-pyrrole-
3-carboxylate (35): a pale-pink solid, mp: decomposed at 236 °C.
1H NMR (500 MHz, DMSO-d6): δ 10.47 (s, 1H, NH), 7.64 (d, J
) 8.05 Hz, 2H), 6.82 (d, J ) 9 Hz, 2H), 3.73 (s, 3H), 3.45 (s, 3H),
2.36 (s, 3H). 13C NMR (125 MHz, DMSO-d6): δ 167.1, 157.1,
142.4, 137.8, 126.0, 125.1, 114.8, 114.6, 113.0, 60.0, 55.8, 14.44.
IR (KBr, cm-1): 3185, 3072, 3000, 2947, 1716, 1695, 1663, 1517,
1441, 1258, 1191, 1077, 1032, 775, 747, 634, 548. Anal. Calcd
for C14H15NO4: C, 64.36; H, 5.79; N, 5.36. Found: C, 64.36; H,
5.82; N, 5.29.
Ethyl 4-Hydroxy-5-(4-methoxyphenyl)-2-methyl-1H-pyrrole-
1
3-carboxylate (36): a pink solid, mp: decomposed at 232 °C. H
Ethyl 4-Hydroxy-5-phenyl-2-propyl-1H-pyrrole-3-carboxylate
1
NMR (500 MHz, DMSO-d6): δ 10.49 (s, 1H, NH), 7.66 (d, J )
7.6 Hz, 2H), 6.82 (t, J ) 8.45 Hz, 2H), 3.91 (q, J ) 7.45 Hz, 2H),
2.35 (s, 3H), 1.09 (t, J ) 6.75 Hz, 3H). 13C NMR (125 MHz,
DMSO-d6): δ 181.5, 163.7, 159.8, 157.7, 129.2, 125.3, 125.0,
114.8, 113.3, 58.8, 55.9, 17.0, 15.1. IR (KBr, cm-1): 3241, 3077,
2974, 1703, 1667, 1518, 1183, 1074, 745. Anal. Calcd for C15H17-
NO4: C, 65.44; H, 6.22; N, 5.09. Found: C, 65.43; H, 6.25; N,
5.08.
(23): a white solid, mp: decomposed at 237 °C. H NMR (500
MHz, DMSO-d6): δ 10.49 (s, 1H, NH), 7.76 (d, J ) 5.65 Hz,
2H), 7.16 (m, 3H), 3.91 (m, 2H), 2.73 (m, 2H), 1.51 (m, 1H), 1.39
(m, 1H), 1.10 (t, J ) 7.05 Hz, 3H), 0.81 (t, J ) 7.05 Hz, 3H). 13
C
NMR (125 MHz, DMSO-d6): δ 166.2, 145.4, 133.8, 132.9, 129.2,
125.1, 124.5, 112.7, 111.6, 56.0, 30.1, 24.2, 15.6, 14.7. IR (KBr,
cm-1): 3237, 3060, 2963, 2932, 2872, 1687, 1653, 1582, 1537,
1510, 1445, 1370, 1180, 1094, 1069, 739, 698. Anal. Calcd for
C16H19NO3: C, 70.31; H, 7.01; N, 5.12. Found: C, 70.12; H, 6.93;
N, 4.98.
tert-Butyl-4-hydroxy-5-(4-methoxyphenyl)-2-methyl-1H-pyr-
role-3-carboxylate (37): a pale-pink solid, mp: decomposed at
1
241 °C. H NMR (500 MHz, DMSO-d6): δ 10.32 (s, 1H, NH),
3-Acetyl-5-(4-fluorophenyl)-4-hydroxy-2-methyl-1H-pyrrol (27):
1
7.66 (d, J ) 8.40 Hz, 2H), 6.82 (d, J ) 8.9 Hz, 2H), 3.71 (s, 3H),
2.31 (s, 3H), 1.30 (s, 9H). 13C NMR (125 MHz, DMSO-d6): δ
171.1, 157.1, 142.4, 137.8, 126.0, 125.1, 114.8, 114.6, 113.0, 81.2,
60.9, 28.9, 14.24. IR (KBr, cm-1): 3241, 3076, 2976, 2935, 2839,
1712, 1647, 1518, 1365, 1333, 1261, 1156, 1080, 1011, 838, 774,
605. Anal. Calcd for C17H21NO4: C, 67.31; H, 6.98; N, 4.62.
Found: C, 67.32; H, 7.04; N, 4.60.
a pale-yellow crystal (ethanol), mp: decomposed at 230 °C. H
NMR (500 MHz, DMSO-d6): δ 10.81 (s, 1H, NH), 7.82 (dd, J )
9.14 Hz, J ) 5.36 Hz, 2H), 7.17 (m, 2H) 2.39 (s, 3H), 2.08 (s,
3H). 13C NMR (125 MHz, DMSO-d6): δ 196.2, 162.0, 132.5, 130.4,
128.1, 118.5, 116.0, 113.5, 112.0, 26.3, 17.1. IR (KBr, cm-1): 3358,
3185, 3060, 1676, 1626, 1513, 1416, 1311, 1237, 1168, 1114, 1086,
999, 950, 813, 760, 606. Anal. Calcd for C13H12FNO2: C, 66.94;
H, 5.19; N, 6.01. Found: C, 67.06; H, 4.98; N, 6.15.
Methyl 5-(4-Fluorophenyl)-4-hydroxy-2-methyl-1H-pyrrole-
3-carboxylate (28): a pale-pink solid, mp: decomposed at 248 °C.
1H NMR (500 MHz, DMSO-d6): δ 10.57 (s, 1H, NH), 7.77 (m,
2H), 7.15 (t, J ) 8.8 Hz, 2H), 3.46 (s, 3H), 2.37 (s, 3H). 13C NMR
(125 MHz, DMSO-d6): δ 167.3, 162.1, 132.8, 130.7, 127.9, 119.0,
116.7, 113.9, 112.1, 51.5, 17.7. IR (KBr, cm-1): 3215, 3080, 2943,
1708, 1663, 1522, 1549, 1498, 1301, 1204, 1176, 1102, 1080, 1022,
811, 739, 598. Anal. Calcd for C13H12FNO3: C, 62.65; H, 4.85;
N, 5.62. Found: C, 62.65; H, 4.92; N, 5.49.
Ethyl 5-(4-fluorophenyl)-4-hydroxy-2-methyl-1H-pyrrole-3-
carboxylate (29): a white solid, decomposed at 234 °C, 1H NMR
(500 MHz, DMSO-d6): δ 10.62 (s, 1H, NH), 7.80 (dd, J ) 5.7
Hz, J ) 7.95 Hz 2H), 7.15 (m, 2H), 3.93 (m, 2H), 2.36 (s, 3H),
1.09 (t, J ) 7.1 Hz 3H). 13C NMR (125 MHz, DMSO-d6): δ 168.1,
162.0, 132.5, 130.4, 128.1, 118.5, 116.0, 113.5, 112.0, 51.1, 17.2,
14.9. IR (KBr, cm-1): 3205, 3072, 2984, 1738, 1551, 1549, 1518,
1333, 1241, 1188, 1112, 1076, 1031, 818, 749, 605. Anal. Calcd
for C14H14FNO3: C, 63.87; H, 5.36; N, 5.32. Found: C, 63.79; H,
5.50; N, 5.28.
Ethyl 4-Hydroxy-5-(4-methoxyphenyl)-2-propyl-1H-pyrrole-
3-carboxylate (38): a pale-pink solid, mp: decomposed at 241 °C.
1H NMR (500 MHz, DMSO-d6): δ 10.43 (s, 1H, NH), 7.68 (d, J
) 7.9 Hz, 2H), 6.81 (d, J ) 8.9 Hz, 2H), 3.97 (m, 2H), 3.71 (s,
3H), 2.78 (m, 2H), 1.48 (m, 1H), 1.35 (m, 1H), 1.11 (t, J ) 7.05
Hz, 3H), 0.81 (t, J ) 7.3 Hz, 3H). 13C NMR (125 MHz, DMSO-
d6): δ 168.3, 157.3, 141.4, 138.1, 126.5, 125.2, 114.7, 114.5, 113.1,
60.1, 55.8, 29.8, 23.9, 15.1, 14.5. IR (KBr, cm-1): 3233, 2968,
1687, 1655, 1539, 1510, 1458, 1261, 1184, 1035, 689. Anal. Calcd
for C17H21NO4: C, 67.31; H, 6.98; N, 4.62. Found: C, 67.22; H,
6.90; N, 4.59.
3-Acetyl-5-(4-bromophenyl)-4-hydroxy-2-methyl-1H-pyrrol
1
(39): a white solid, mp: decomposed at 244 °C. H NMR (500
MHz, DMSO-d6): δ 10.81 (s, 1H, NH), 9.68 (s, 1H, OH), 7.66 (d,
J ) 8.2 Hz, 2H), 7.53 (t, J ) 8.6 Hz, 2H), 2.31 (s, 3H), 2.14 (s,
3H). 13C NMR (125 MHz, DMSO-d6): δ 198.7, 136.0, 132.9, 132.3,
131.1, 127.0, 118.2, 113.8, 112.1, 23.9, 15.3. IR (KBr, cm-1): 3294,
2976, 2919, 1631, 1538, 1502, 1426, 1333, 1176, 999, 814, 774,
629. Anal. Calcd for C13H12BrNO2: C, 53.08; H, 4.11; N, 4.76.
Found: C, 53.17; H, 4.15; N, 4.78.
Methyl 5-(4-Bromophenyl)-4-hydroxy-2-methyl-1H-pyrrole-
3-carboxylate (40): a pale-pink solid, mp: decomposed at 270 °C,
1H NMR (500 MHz, DMSO-d6): δ 10.54 (s, 1H, NH), 7.64 (d, J
) 8.15 Hz, 2H), 7.53 (d, J ) 8.45 Hz, 2H), 3.47 (s, 3H), 2.38 (s,
3H). 13C NMR (125 MHz, DMSO-d6): δ 167.1, 135.9, 132.7, 131.8,
130.0, 126.1, 117.9, 113.1, 111.3, 51.9, 17.7. IR (KBr, cm-1): 3213,
tert-Butyl-5-(4-fluorophenyl)-4-hydroxy-2-methyl-1H-pyrrole-
3-carboxylate (30): a pale-gray solid, mp: decomposed at 226 °C.
1H NMR (500 MHz, DMSO-d): δ 10.45 (s, 1H, NH), 7.80 (dd, J
) 9.1 Hz, J ) 5.48 Hz, 2H), 7.16 (m, 2H) 2.32 (s, 3H), 1.30 (s,
9H). 13C NMR (125 MHz, DMSO-d6): δ 171.1, 162.0, 132.5, 130.4,
128.1, 118.5, 116.0, 113.5, 112.0, 80.9, 28.3, 14.2. IR (KBr, cm-1):
2094 J. Org. Chem., Vol. 73, No. 6, 2008

Synthesis of New 2-Alkyl-5-aryl-(1H)-pyrrole-4-ol
3076, 2981, 2951, 1708, 1655, 1547, 1510, 1442, 1196, 1084, 1007,
762, 613. Anal. Calcd for C13H12BrNO3: C, 50.34; H, 3.90; Br,
25.76; N, 4.52. Found: C, 50.32; H, 4.01; N, 4.43.
1705, 1647, 1506, 1344, 1183, 759, 681. Anal. Calcd for C18H26-
ClNO3: C, 63.61; H, 7.71; N, 4.12. Found: C, 63.52; H, 7.78; N,
4.11.
Ethyl 5-(4-Bromophenyl)-4-hydroxy-2-methyl-1H-pyrrole-3-
carboxylate (41): a pink solid, mp: decomposed at 245 °C. H
3-Acetyl-5-biphenyl-4-yl-4-hydroxy-2-methyl-1H-pyrrol (48):
a dark-brown solid, mp: decomposed at 233 °C. H NMR (500
1
1
NMR (500 MHz, DMSO-d6): δ 10.59 (s, 1H, NH), 7.68 (d, J )
8.25 Hz, 2H), 7.52 (d, J ) 8.65 Hz, 2H), 3.94 (m, 2H), 2.37 (s,
3H), 1.10 (t, J ) 7.05 Hz, 3H). 13C NMR (125 MHz, DMSO-d6):
δ 167.3, 136.9, 132.1, 131.4, 129.3, 125.4, 117.2, 112.4, 110.7,
51.6, 17.7, 14.1. IR (KBr, cm-1): 3196, 3068, 2980, 1705, 1651,
1542, 1513, 1397, 1328, 1187, 1080, 1034, 753, 689, 602. Anal.
Calcd for C14H14BrNO3: C, 51.87; H, 4.35; N, 4.32. Found: C,
51.87; H, 4.28; N, 4.39.
MHz, DMSO-d6): δ 10.87 (s, 1H, NH), 7.90 (d, J ) 7.15 Hz,
2H), 7.68 (d, J ) 6.95 Hz, 2H), 7.65 (d, J ) 7.75 Hz, 2H), 7.46 (t,
J ) 6.55 Hz, 2H), 7.38 (t, J ) 6.65 Hz, 1H), 2.44 (s, 3H), 2.10 (s,
3H). 13C NMR (125 MHz, DMSO-d6): δ 197.8, 141.8, 141.2, 132.9,
130.7, 129.9, 129.8, 129.2, 128.6, 127.9, 127.4, 124.8, 102.7, 24.3,
17.2. IR (KBr, cm-1): 3394, 3068, 3036, 1671, 1635, 1498, 1410,
1313, 1168, 750. Anal. Calcd for C19H17NO2: C, 78.33; H, 5.88;
N, 4.81. Found: C, 78.22; H, 5.89; N, 4.78.
Ethyl 5-(4-Bromophenyl)-4-hydroxy-2-propyl-1H-pyrrole-3-
carboxylate (42): a pink solid, mp: decomposed at 235 °C. H
Methyl 5-Biphenyl-4-yl-4-hydroxy-2-methyl-1H-pyrrole-3-
carboxylate (49): a cream solid, mp: decomposed at 225 °C. H
1
1
NMR (500 MHz, DMSO-d6): δ 10.51 (s, 1H, NH), 7.66 (d, J )
8.3 Hz, 2H), 7.51 (d, J ) 8.7 Hz, 2H), 3.95 (m, 2H), 2.75 (m, 2H),
1.45 (m, 1H), 1.37 (m, 1H), 1.11 (t, J ) 7.15 Hz, 3H), 0.80 (t, J
) 7.35 Hz, 3H). 13C NMR (125 MHz, DMSO-d6): δ 167.3, 134.9,
132.0, 130.9, 130.2, 125.9, 117.2, 113.4, 112.1, 51.8, 17.7, 14.1.
IR (KBr, cm-1): 3241, 3068, 2972, 1694, 1650, 1510, 1397, 1336,
1180, 1082, 1007, 753, 682. Anal. Calcd for C16H18BrNO3: C,
54.56; H, 5.15; N, 3.98. Found: C, 54.59; H, 5.07; N, 4.11.
NMR (500 MHz, DMSO-d6): δ 10.61 (s, 1H, NH), 7.83 (m, 2H),
7.68 (d, J ) 6.8 Hz, 2H), 7.63 (d, J ) 7.6 Hz, 2H), 7.46 (t, J )
6.83 Hz, 2H), 7.37 (m, 1H), 3.33 (s, 3H), 2.42 (s, 3H). 13C NMR
(125 MHz, DMSO-d6): δ 164.0, 141.3, 140.8, 133.7, 130.8, 129.9,
129.0, 128.8, 127.6, 127.1, 126.4, 124.3, 101.7, 59.6, 17.8. IR (KBr,
cm-1): 3221, 3072, 2951, 1709, 1664, 1518, 1441, 1337, 1196,
1079, 1034, 755. Anal. Calcd for C19H17NO3: C, 74.25; H, 5.58;
N, 4.56. Found: C, 74.25; H, 5.63; N, 4.40.
3-Acetyl-5-(4-chlorophenyl)-4-hydroxy-2-methyl-1H-pyrrol (43):
a pink solid, mp: decomposed at 261 °C. H NMR (500 MHz,
Ethyl 5-Biphenyl-4-yl-4-hydroxy-2-methyl-1H-pyrrole-3-car-
boxylate (50): a cream solid, mp: decomposed at 233 °C. 1H NMR
(500 MHz, DMSO-d6): δ 10.68 (s, 1H, NH), 7.86 (m, 2H), 7.68
(d, J ) 6.9 Hz, 2H), 7.63 (d, J ) 7.7 Hz, 2H), 7.45 (t, J ) 6.85
Hz, 2H), 7.38 (m, 1H), 3.90 (q, J ) 6.8 Hz, 2H), 2.37 (s, 3H),
1.07 (t, J ) 6.6 Hz, 3H). 13C NMR (125 MHz, DMSO-d6): δ 163.6,
140.5, 140.0, 132.5, 129.8, 129.7, 128.6, 128.5, 127.4, 127.0, 126.1,
123.9, 100.7, 58.9, 17.1, 15.1. IR (KBr, cm-1): 3213, 3061, 2977,
1724, 1659, 1514, 1196, 753. Anal. Calcd for C20H19NO3: C, 74.75;
H, 5.96; N, 4.36. Found: C, 74.75; H, 5.89; N, 4.35.
1
DMSO-d6): δ 10.83 (s, 1H, NH), 7.87 (d, J ) 7.9 Hz, 2H), 7.42
(d, J ) 8.35 Hz, 2H), 2.40 (s, 3H), 2.10 (s, 3H). 13C NMR (125
MHz, DMSO-d6): δ 197.5, 145.0, 136.6, 133.8, 129.6, 128.2, 123.7,
111.3, 106.3, 23.7, 14.7. IR (KBr, cm-1): 3302, 3068, 1639, 1547,
1498, 1325, 1096, 1019, 818, 621. Anal. Calcd for C13H12ClNO2:
C, 62.53; H, 4.84; N, 5.61. Found: C, 62.48; H, 4.82; N, 5.69.
Methyl 5-(4-Chlorophenyl)-4-hydroxy-2-methyl-1H-pyrrole-
1
3-carboxylate (44): a pink solid, mp: decomposed at 261 °C. H
NMR (500 MHz, DMSO-d6): δ 10.55 (s, 1H, NH), 7.71 (d, J )
7.6 Hz, 2H), 7.38 (d, J ) 8.1 Hz, 2H), 3.35 (s, 3H), 2.23 (s, 3H).
13C NMR (125 MHz, DMSO-d6): δ 165.9, 144.9, 138.1, 133.4,
129.9, 129.0, 125.3, 112.7, 104.8, 61.1, 17.9. IR (KBr, cm-1): 3229,
3076, 2943, 1704, 1647, 1510, 1192, 1072, 745. Anal. Calcd for
C13H12ClNO3: C, 58.77; H, 4.55; N, 5.27. Found: C, 58.78; H,
4.58; N, 5.20.
Ethyl 5-(4-Chlorophenyl)-4-hydroxy-2-methyl-1H-pyrrole-3-
carboxylate (45): a pale-pink solid, mp: decomposed at 244 °C.
1H NMR (500 MHz, DMSO-d6): δ 10.61 (s, 1H, NH), 7.75 (d, J
) 8.15 Hz, 2H), 7.39 (d, J ) 8.65 Hz, 2H), 3.94 (m, 2H), 2.37 (s,
3H), 1.10 (t, J ) 7.1 Hz, 3H). 13C NMR (125 MHz, DMSO-d6):
δ 163.8, 144.8, 137.2, 133.0, 129.3, 128.8, 124.9, 112.0, 103.1,
58.7, 17.9, 15.8. IR (KBr, cm-1): 3194, 3071, 2987, 2879, 1712,
1648, 1548, 1516, 1436, 1266, 1186, 1095, 1031, 755, 703, 635,
607. Anal. Calcd for C14H14ClNO3: C, 60.11; H, 5.04; N, 5.01.
Found: C, 60.15; H, 5.00; N, 5.11.
tert-Butyl-5-(4-chlorophenyl)-4-hydroxy-2-methyl-1H-pyrrole-
3-carboxylate (46): a pale-pink solid, mp: decomposed at 238 °C.
1H NMR (500 MHz, DMSO-d6): δ 10.47 (s, 1H, NH), 7.76 (d, J
) 8.25 Hz, 2H), 7.38 (d, J ) 8.5 Hz, 2H), 2.35 (s, 3H), 1.31 (s,
9H). 13C NMR (125 MHz, DMSO-d6): δ 171.3, 144.8, 137.0, 133.0,
129.31, 128.8, 124.9, 112.1, 102.9, 81.3, 28.9, 14.3. IR (KBr, cm-1):
3217, 3080, 2980, 1708, 1651, 1514, 1402, 1156, 1003, 758. Anal.
Calcd for C16H18ClNO3: C, 62.44; H, 5.89; N, 4.55. Found: C,
62.32; H, 5.73; N, 4.59.
tert-Butyl-5-biphenyl-4-yl-4-hydroxy-2-methyl-1H-pyrrole-3-
carboxylate (51): a pale-cream solid, mp: decomposed at 235 °C.
1H NMR (500 MHz, DMSO-d6): δ 10.49 (s, 1H, NH), 7.86 (m,
2H), 7.66 (d, J ) 6.9 Hz, 2H), 7.61 (d, J ) 7.7 Hz, 2H), 7.46 (t,
J ) 6.85 Hz, 2H), 7.37 (m, 1H), 2.36 (s, 3H), 1.27 (s, 9H). 13C
NMR (125 MHz, DMSO-d6): δ 168.2, 141.3, 140.8, 133.7, 130.8,
129.9, 129.0, 128.8, 127.6, 127.1, 126.4, 124.3, 101.7, 81.1, 28.7,
14.9. IR (KBr, cm-1): 3241, 3072, 2976, 1706, 1651, 1513, 1349,
1157, 1079, 1003, 841, 756. Anal. Calcd for C22H23NO3: C, 75.62;
H, 6.63; N, 4.01. Found: C, 75.55; H, 6.58; N, 3.88.
2-Benzoyl-5(or 4)-phenyl-1H-imidazol (55): a yellow solid. 1H
NMR (500 MHz, DMSO-d6): δ 13.80 (s, 0.25H, NH), 13.63 (s,
1H, NH), 8.60 (d, J ) 7.76 Hz, 2H), 8.47 (d, J ) 7.7 Hz, 0.5H),
8.08 (s, 1H), 7.97 (d, J ) 7.95 Hz, 0.5H), 7.94 (d, J ) 7.64 Hz,
2H), 7.79 (s, 0.25H), 7.69 (t, J ) 7.1 Hz, 1H), 7.66 (t, J ) 7.6 Hz,
0.25H), 7.60 (t, J ) 7.6 Hz, 2H), 7.57 (t, J ) 8.1 Hz, 0.5H), 7.47
(t, J ) 7.55 Hz, 0.5H), 7.42 (t, J ) 7.7 Hz, 2H), 7.37 (t, J ) 7.1
Hz, 0.25H), 7.28 (t, J ) 7.3 Hz, 1H). 13C NMR (125 MHz, DMSO-
d6): δ 181.6, 146.6, 145.5, 143.7, 137.0, 136.8, 136.6, 134.5, 133.9,
133.7, 131.5, 131.4, 129.8, 129.5, 129.1, 129.0, 128.0, 126.5, 125.7,
119.5. IR (KBr, cm-1): 3270, 1621, 1454, 1280, 1164, 906, 771,
687. Anal. Calcd for C16H12N2O: C, 77.40; H, 4.87; N, 11.28.
Found: C, 77.39; H, 4.73; N, 11.17.
Acknowledgment. We thank the Research Office of Sharif
University of Technology for financial support and Mrs. M.
Aghazadeh (Department of Chemistry, Sharif University of
Technology) for taking NMR spectra.
Ethyl 5-(4-Chlorophenyl)-4-hydroxy-2-propyl-1H-pyrrole-3-
1
carboxylate (47): a pink solid, mp: decomposed at 241 °C. H
NMR (500 MHz, DMSO-d6): δ 10.51 (s, 1H, NH), 7.74 (d, J )
7.6 Hz, 2H), 7.38 (d, J ) 8.1 Hz, 2H), 3.95 (q, J ) 7.35 Hz, 2H),
2.75 (m, 2H), 1.47 (m, 1H), 1.34 (m, 1H), 1.11 (t, J ) 6.2 Hz,
3H), 0.80 (t, J ) 6.65 Hz, 3H). 13C NMR (125 MHz, DMSO-d6):
δ 163.8, 144.8, 137.2, 133.0, 129.3, 128.8, 124.9, 112.0, 103.1,
56.1, 30.7, 23.8, 15.7, 14.3. IR (KBr, cm-1): 3245, 3071, 2974,
Supporting Information Available: Preparation procedures, 1H
NMR spectra of compounds 19-23, 27-31, 35-51, and 55. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
JO702385N
J. Org. Chem, Vol. 73, No. 6, 2008 2095