A Novel Approach to the Synthesis of Highly Functionalized Pyrroles

Abstract

A new and efficient one-pot synthesis of polysubstituted pyrrole derivatives by a three-component reaction between dialkyl acetylenedicarboxylates, aromatic amines, triphenylphosphine, and arylglyoxals is described. The reactions were performed in dichloro­methane at room temperature and neutral conditions and afforded high yields of products.

Simple nitrogen-containing heterocycles receive considerable attention in the literature as a consequence of their exciting biological properties and their role as pharmacophores of historical importance. [¹] Of these heterocycles, the synthesis, reactions, and biological activities of ­pyrrole-containing molecules stand as an area of research in heteroaromatic chemistry, and this structural motif appears in a large number of pharmaceutical agents and natural products. [²] Accordingly, many strategies have been developed for the preparation of pyrroles. [²] [³]

Addition reaction between phosphines and activated ­carbon-carbon triple bonds is well known to produce a ­reactive zwitterionic intermediate, which may be trapped by various electrophiles. [4-8] Reaction of triphenylphosphine with dimethyl acetylenedicarboxylate (DMAD) has been studied in the presence of a variety of organic acidic compounds, in order to trap the zwitterionic intermediate. Trapping of Ph₃P-DMAD zwitterion by an organic acidic compound containing a carbonyl group has been used as a one-pot and efficient route for the synthesis of a variety of heterocyclic and carbocyclic compounds. [7-¹¹] Treatment of triphenylphosphine with DMAD in the presence of primary amines has been reported to produce β-amino phosphoranes 4 (Scheme  [¹] ). [8] Recently, we reported the reaction of these ylides with ethyl chlorooxoacetate for the synthesis of dimethyl N-aryl-4-ethoxy-5-oxo-2,5-dihydro-1H-pyrrole-2,3-dicarboxylates. [¹²] In continuation of our previous works on the reaction between phosphorus nucleophiles and acetylenic esters in the presence of organic acids, [6] [9] [¹¹] [¹²] we decided to investigate the reaction of these phosphorus ylides with arylglyoxals.

Ylide 4 was prepared by the reaction between triphenylphosphine, DMAD, and aniline by the previously reported procedure. [8] When phosphorane 4 was stirred with an equimolar amount of 4-nitrophenylglyoxal in dichloromethane, a smooth reaction took place. After completion of the reaction (monitored by TLC) dimethyl 5-(4-nitrophenyl)-1-phenylpyrrole-2,3-dicarboxylate (6a) was obtained in 90% yield. As shown in Scheme  [²] , it is reasonable to assume that the Wittig reaction of phosphorane 4 with 4-nitrophenylglyoxal (5) affords intermediate 6 which then cyclizes to dihydropyrrole intermediate 7 that subsequently loses water to produce pyrrole derivative 6a.

Being successful in this reaction, we decided to investigate the one-pot synthesis of dimethyl 5-(4-nitrophenyl)-1-phenylpyrrole-2,3-dicarboxylate (6a, Table  [¹] ). Thus, equimolar amounts of triphenylphosphine, aniline, and DMAD were mixed in dichloromethane as solvent. After stirring for one minute at room temperature, 4-nitrophenylglyoxal was added, and the progress of the reaction was monitored by TLC. After 24 hours the TLC of the mixture of the reaction showed only the presence of pyrrole derivative 6a and triphenylphosphine oxide. Silica gel chromatography afforded the product dimethyl 5-(4-nitrophenyl)-1-phenylpyrrole-2,3-dicarboxylate (6a) in 85% yield. [¹³]

To investigate the scope of the reaction, different aryl amines and arylglyoxals were reacted with triphenylphosphine and dialkyl acetylenedicarboxylates (DAAD) and the corresponding pyrroles were obtained in good yields (Table  [¹] ).

Table 1 Three-Component Reaction between Anilines, DAAD, and Arylglyoxals Promoted by Ph₃P

2, 6	R	E	Ar	Yield of 6 (%)a
a	Ph	CO2Me	4-O2NC6H4	85
b	4-MeC6H4	CO2Me	4-O2NC6H4	85
c	4-MeC6H4	CO2 t-Bu	4-ON2C6H4	85
d	4-MeC6H4	CO2Me	4-BrC6H4	84
e	4-MeC6H4	CO2Et	4-BrC6H4	85
f	4-MeOC6H4	CO2Me	4-O2NC6H4	86
g	4-MeOC6H4	CO2Et	4-BrC6H4	90
h	4-ClC6H4	CO2Me	4-BrC6H4	85
a Isolated yields.

The structure of compounds 6a-h was deduced from their elemental analyses and their IR, ^¹H NMR, and ^¹³C NMR spectra. [¹4-²¹] The mass spectrum of compound 6a displayed the molecular ion peak at m/z = 380 as the base peak. The 500 MHz ^¹H NMR spectrum of 6a exhibited three sharp signals at δ = 3.72, 3.85, and 7.09 ppm for two methoxy group protons and the proton of pyrrole ring, respectively. Aromatic protons resonated between δ = 7.34 and 8.20 ppm. The ^¹³C NMR spectrum of compound 6a showed sixteen distinct resonances in agreement with the proposed structure. The structural assignments made on the basis of the NMR spectra of compound 6a were supported by its IR spectrum. The ester carbonyl groups exhibited strong absorption bands at 1716 and 1720 cm^-¹.

In conclusion, we report a three-component reaction between dialkyl acetylenedicarboxylates, aromatic amines, and arylglyoxals promoted by triphenylphosphine to produce functionalized pyrrole derivatives in high yields. The present method carries the advantage that not only the reaction is performed under neutral conditions but also that the substances can be mixed without any activation or modification.

References and Notes

• 1 Yates FS. In Comprehensive Heterocyclic Chemistry   Vol. 2:  Boulton AJ. McKillop A. Pergamon; Oxford: 1984.  p.511 
  Search in Google Scholar
• 2 Jones RA. In Pyrroles: The synthesis, Reactivity, and Physical Properties of Substituted Pyrroles   Part 2:  Wiley; New York: 1992. 
  Search in Google Scholar
• 3 Gilchrist TL. J. Chem. Soc., Perkin Trans. 1  2001,  2491 
  Crossref
• 4 Trost BM. Dake GR. J. Am. Chem. Soc.  1997,  119:  7595 
  CrossrefSearch in Google Scholar
• 5 Nair V. Nair JS. Vinod AU. Rath NP. J. Chem. Soc., Perkin Trans. 1  1997,  329 
• 6 Anary-Abbasinejad M. Anaraki-Ardakani H. Hosseini-Mehdiabad H. Phosphorus, Sulfur Silicon Relat. Elem.  2008,  183:  1440 
  CrossrefSearch in Google Scholar
• 7 Yavari I. Hekmat-Shoar R. Zonouzi A. Tetrahedron Lett.  1998,  39:  2391 
  CrossrefSearch in Google Scholar
• 8 Yavari I. Adib M. Hojabri L. Tetrahedron  2002,  58:  7213 
  CrossrefSearch in Google Scholar
• 9 Anary-Abbasinejad M. Mosslemin MH. Hassanabadi A. Tabatabaee M. Synth. Commun.  2008,  38:  3700 
  CrossrefSearch in Google Scholar
• 10 Evans LA. Griffiths KE. Guthmann H. Murphy PJ. Tetrahedron Lett.  2002,  43:  299 
  CrossrefSearch in Google Scholar
• 11 Mosslemin MH. Yavari I. Anary-Abbasinejad M. Nateghi MR. Synthesis  2004,  1029 
  Thieme Connect
• 12 Anary-Abbasinejad M. Anaraki-Ardakani H. Dehghan A. Hassanabadi A. Seyedmir MR. J. Chem. Res.  2007,  574 
  Crossref

General Procedure for the Preparation of Compounds 6a-h
To a magnetically stirred solution of Ph₃P (1 mmol) and aniline derivative (1 mmol) in CH₂Cl₂ (10 mL) was added dropwise a mixture of dialkyl acetylenedicarboxylate (1 mmol) in CH₂Cl₂ (3 mL) at r.t. over 2 min. The reaction mixture was then stirred for one more minute. Arylglyoxal (1 mmol) was added, and the reaction mixture was stirred for more 24 h. Solvent was evaporated, and the residue was purified by column chromatography on SiO₂ using EtOAc-hexane (1:4) mixture as eluent.

Dimethyl 5-(4-Nitrophenyl)-1-(phenyl)-pyrrole-2,3-dicarboxylate (6a)
Yellow powder, mp 115-117 ˚C. IR (KBr): ν_max = 1716, 1720 (C=O) cm^-¹. Anal. Calcd (%) for C₂₀H₁₆N₂O₆ (380.35): C, 63.16; H, 4.24; N, 7.37. Found: C, 63.27; H, 4.19; N, 7.65. ^¹H NMR (500 MHz, CDCl₃): δ = 3.72 and 3.85 (6 H, 2 s, 2 OCH₃), 7.09 (1 H, s, CH of pyrrole), 7.34 (2 H, m, 2 CH of C₆H₅), 7.48 (3 H, m, 3 CH of C₆H₅), 7.58 (2 H, d, J = 9 Hz, 2 CH of C₆H₄NO₂), 8.20 (2 H, d, J = 9 Hz, 2 CH of C₆H₄NO₂). ^¹³C NMR (125.8 MH_Z, CDCl₃): δ = 52.6 and 52.9 (2 OCH₃), 121.2, 123.3, 124.3, 125.4, 126.3, 126.6, 128.8, 129.3, 129.6, 139.3, 140.5, 147.1 (arom.), 160.8 and 166.3 (2 C=O, ester). MS: m/z (%) = 380 (100) [M⁺ ].

Dimethyl 1-(4-Methylphenyl)-5-(4-nitrophenyl)-pyrrole-2,3-dicarboxylate (6b)
Yellow powder, mp 148-150 ˚C. IR (KBr): ν_max = 1717 (C=O) cm^-¹. Anal. Calcd (%) for C₂₁H₁₈N₂O₆ (394.38): C, 63.96; H, 4.60; N, 7.10. Found: C, 63.67; H, 4.71; N, 7.29. ^¹H NMR (500 MHz, CDCl₃): δ = 2.24 (3 H, s, CH₃), 3.55 and 3.67 (6 H, 2 S, 2 OCH₃), 6.87 (1 H, s, CH pyrrol), 7.07 (4 H, m, arom.), 7.41 (2 H, d, J = 9 Hz, 2 CH arom.), 8.05 (2 H, d, J = 9 Hz, 2 CH arom.). ^¹³C NMR (500 MHz, CDCl₃): δ = 21.2 (CH₃), 52.2 and 52.5 (2 OCH₃), 120.6, 122.7, 123.9, 125.7, 126.2, 128.3, 129.7, 131.1, 136.4, 139.0, 140.1, 146.7 (arom.), 160.4, 166.7 (2 C=O, ester). MS: m/z (%) = 394 (100) [M⁺ ].

Di( tert -butyl) 1-(4-Methylphenyl)-5-(4-nitrophenyl)-pyrrole-2,3-dicarboxylate (6c)
Yellow oil. IR (KBr): ν_max = 1709 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₇H₃₀N₂O₆ (478.54): C, 67.77; H, 6.32; N, 5.85. Found: C, 67.92; H, 6.10; N, 5.97. ^¹H NMR (500 MHz, CDCl₃): δ = 1.31 (9 H, s, t-Bu), 1.48 (9 H, s, t-Bu), 2.41 (3 H, s, CH₃₎, 6.91 (1 H, s, CH pyrrole(, 7.19 (4 H, m, arom.), 7.58 and 8.20 (4 H, 2 d, ^³ J _HH = 8 Hz, arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 21.5 (CH₃), 28.2 and 28.4 (6 CH₃ of 2 t-Bu), 82.3 and 82.7 (2 C of 2 t-Bu), 121.5, 123.2, 124.0, 125.1, 126.2, 128.1, 129.2, 130.0, 137.5, 139.0, 141.4, 146.9 (arom.), 159.6 and 164.5 (2 C=O, ester). MS: m/z (%) = 478 (90) [M⁺ ].

Dimethyl 5-(4-Bromophenyl)-1-(4-methylphenyl)-pyrrole-2,3-dicarboxylate (6d)
Yellow oil. IR (KBr): ν_max = 1719 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₁H₁₈BrNO₄ (428.28): C, 58.89; H, 4.24; N, 3.27. Found: C, 58.97; H, 4.19; N, 3.55. ^¹H NMR (500 MHz, CDCl₃): δ = 2.41 (3 H, s, CH₃), 3.72 and 3.83 (6 H, 2 s, 2 OCH₃), 6.95 (1 H, s, CH pyrrole), 7.22 (4 H, m, 4 CH arom.), 7.30 (2 H, d, J = 9 Hz, 2 CH arom.), 7.49 (2 H, d, J = 9 Hz, 2 CH arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 21.6 (CH₃), 52.5 and 52.8 (2 OCH₃), 121.4, 121.6, 124.1, 124.4, 126.1, 126.2, 129.9, 130.0, 132.1, 132.7, 137.2, 139.1 (arom.), 160.9 and 166.8 (2 C=O, ester). MS: m/z (%) = 427 (95) [M⁺ ].

Diethyl 5-(4-Bromophenyl)-1-(4-methylphenyl)-pyrrole-2,3-dicarboxylate (6e)
Yellow oil. IR (KBr): ν_max = 1720 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₃H₂₂BrNO₄ (456.33): C, 60.54; H, 4.86; N, 3.07. Found: C, 60.29; H, 4.69; N, 3.31. ^¹H NMR (500 MHz, CDCl₃): δ = 1.17 and 1.30 (6 H, 2 t, ^³ J _HH = 7 Hz, 2 CH₃), 2.42 (3 H, s, CH₃), 4.16 and 4.31 (4 H, 2 q, ^³ J _HH = 7 Hz, 2 OCH₂)_, 6.93 (1 H, s, CH pyrrole), 7.22 (4 H, m, 4 CH arom.), 7.32 (2 H, d, J = 9 Hz, 2 CH arom.), 7.48 (2 H, d, J = 9 Hz, 2 CH arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.3, 14.6 and 21.6 (3 CH₃), 61.4 and 61.7 (2 OCH₂), 121.5, 121.6, 124.0, 124.5, 126.0, 126.3, 128.9, 130.2, 132.0, 132.8, 137.3, 139.0 (arom.), 160.4 and 166.3 (2 C=O, ester). MS: m/z (%) = 455 (77) [M⁺ ].

Dimethyl 1-(4-Methoxyphenyl)-5-(4-nitrophenyl)-pyrrole-2,3-dicarboxylate (6f)
Yellow powder; mp 159-161 ˚C. IR (KBr): ν_max = 1731, 1729 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₁H₁₈N₂O₇ (410.38): C, 61.46; H, 4.42; N, 6.83. Found: C, 61.52; H, 4.19; N, 7.07. ^¹H NMR (500 MHz, CDCl₃): δ = 3.73 and 3.85 (6 H, 2 s, 2 OCH₃), 3.86 (3 H, s, OCH₃), 7.05 (1 H, s, CH pyrrole), 6.95 (2 H, d, J = 8 Hz, 2 CH arom.), 7.28 (2 H, d, J = 8 Hz, 2 CH arom.), 7.60 (2 H, d, J = 8 Hz, 2 CH arom.), 8.22 (2 H, d, J = 8 Hz, 2 CH arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 52.6 and 52.9 (2 OCH₃), 56.0 (OCH₃), 114.6, 116.9, 120.9, 123.0, 124.3, 126.9, 127.6, 128.7, 132.2, 140.6, 147.1, 160.23 (arom.), 160.8 and 166.4 (2 C=O, ester). MS: m/z (%) = 410 (61) [M⁺ ].

Diethyl 5-(4-Bromophenyl)-1-(4-methoxyphenyl)-pyrrole-2,3-dicarboxylate (6g)
Yellow powder; mp 149-151 ˚C. IR (KBr): ν_max = 1714, 1711 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₃H₂₂BrNO₅ (472.33): C, 58.49; H, 4.69; N, 2.97. Found: C, 58.25; H, 4.51; N, 3.11. ^¹H NMR (500 MH_Z, CDCl₃): δ = 1.16 and 1.27 (6 H, 2 t, ^³ J _HH = 7 Hz, 2 CH₃), 3.82 (3 H, s, OCH₃), 4.15 and 4.29 (4 H, 2 q, ^³ J _HH = 7 Hz, 2 OCH₂)_, 6.91 (1 H, s, CH pyrrole), 6.92, 7.24, 7.30 and 7.46 (8 H, 4 d, ^³ J _HH = 8 H_Z, arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.3 and 14.5 (2 CH₃), 55.9 (OCH₃), 61.3 and 61.8 (2 OCH₂), 114.4, 116.9, 121.4, 123.8, 124.6, 126.2, 127.7, 129.9, 132.0, 132.7, 132.8 and 160.1 (arom.), 160.4 and 166.4 (2 C=O, ester). MS: m/z (%) = 471 (73) [M⁺ ].

Dimethyl 5-(4-Bromophenyl)-1-(4-chlorophenyl)-pyrrole-2,3-dicarboxylate (6h)
Yellow oil. IR (KBr): ν_max = 1718 (C=O) cm^-¹. Anal. Calcd (%) for C₂₀H₁₅BrClNO₄ (448.69): C, 53.54; H, 3.37; N, 3.12. Found: C, 53.20; H, 3.19; N, 3.35. ^¹H NMR (500 MHz, CDCl₃): δ = 3.72 and 3.84 (6 H, 2 s, 2 OCH₃), 6.94 (1 H, s, CH of pyrrole), 7.29 (4 H, m, 4 CH arom.), 7.42 (2 H, d, J = 9 Hz, 2 CH arom.), 7.50 (2 H, d, J = 9 Hz, 2 CH arom.). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 52.5 and 52.9 (2 OCH₃), 121.8, 122.3, 123.9, 124.5, 126.1, 127.9, 129.6, 129.8, 132.3, 132.6, 135.0, 138.2 (arom.), 160.6 and 166.7 (2 C=O, ester). MS: m/z (%) = 447 (37) [M⁺ ].

References and Notes

• 1 Yates FS. In Comprehensive Heterocyclic Chemistry   Vol. 2:  Boulton AJ. McKillop A. Pergamon; Oxford: 1984.  p.511 
  Search in Google Scholar
• 2 Jones RA. In Pyrroles: The synthesis, Reactivity, and Physical Properties of Substituted Pyrroles   Part 2:  Wiley; New York: 1992. 
  Search in Google Scholar
• 3 Gilchrist TL. J. Chem. Soc., Perkin Trans. 1  2001,  2491 
  Crossref
• 4 Trost BM. Dake GR. J. Am. Chem. Soc.  1997,  119:  7595 
  CrossrefSearch in Google Scholar
• 5 Nair V. Nair JS. Vinod AU. Rath NP. J. Chem. Soc., Perkin Trans. 1  1997,  329 
• 6 Anary-Abbasinejad M. Anaraki-Ardakani H. Hosseini-Mehdiabad H. Phosphorus, Sulfur Silicon Relat. Elem.  2008,  183:  1440 
  CrossrefSearch in Google Scholar
• 7 Yavari I. Hekmat-Shoar R. Zonouzi A. Tetrahedron Lett.  1998,  39:  2391 
  CrossrefSearch in Google Scholar
• 8 Yavari I. Adib M. Hojabri L. Tetrahedron  2002,  58:  7213 
  CrossrefSearch in Google Scholar
• 9 Anary-Abbasinejad M. Mosslemin MH. Hassanabadi A. Tabatabaee M. Synth. Commun.  2008,  38:  3700 
  CrossrefSearch in Google Scholar
• 10 Evans LA. Griffiths KE. Guthmann H. Murphy PJ. Tetrahedron Lett.  2002,  43:  299 
  CrossrefSearch in Google Scholar
• 11 Mosslemin MH. Yavari I. Anary-Abbasinejad M. Nateghi MR. Synthesis  2004,  1029 
  Thieme Connect
• 12 Anary-Abbasinejad M. Anaraki-Ardakani H. Dehghan A. Hassanabadi A. Seyedmir MR. J. Chem. Res.  2007,  574 
  Crossref

General Procedure for the Preparation of Compounds 6a-h
To a magnetically stirred solution of Ph₃P (1 mmol) and aniline derivative (1 mmol) in CH₂Cl₂ (10 mL) was added dropwise a mixture of dialkyl acetylenedicarboxylate (1 mmol) in CH₂Cl₂ (3 mL) at r.t. over 2 min. The reaction mixture was then stirred for one more minute. Arylglyoxal (1 mmol) was added, and the reaction mixture was stirred for more 24 h. Solvent was evaporated, and the residue was purified by column chromatography on SiO₂ using EtOAc-hexane (1:4) mixture as eluent.

Dimethyl 5-(4-Nitrophenyl)-1-(phenyl)-pyrrole-2,3-dicarboxylate (6a)
Yellow powder, mp 115-117 ˚C. IR (KBr): ν_max = 1716, 1720 (C=O) cm^-¹. Anal. Calcd (%) for C₂₀H₁₆N₂O₆ (380.35): C, 63.16; H, 4.24; N, 7.37. Found: C, 63.27; H, 4.19; N, 7.65. ^¹H NMR (500 MHz, CDCl₃): δ = 3.72 and 3.85 (6 H, 2 s, 2 OCH₃), 7.09 (1 H, s, CH of pyrrole), 7.34 (2 H, m, 2 CH of C₆H₅), 7.48 (3 H, m, 3 CH of C₆H₅), 7.58 (2 H, d, J = 9 Hz, 2 CH of C₆H₄NO₂), 8.20 (2 H, d, J = 9 Hz, 2 CH of C₆H₄NO₂). ^¹³C NMR (125.8 MH_Z, CDCl₃): δ = 52.6 and 52.9 (2 OCH₃), 121.2, 123.3, 124.3, 125.4, 126.3, 126.6, 128.8, 129.3, 129.6, 139.3, 140.5, 147.1 (arom.), 160.8 and 166.3 (2 C=O, ester). MS: m/z (%) = 380 (100) [M⁺ ].

Dimethyl 1-(4-Methylphenyl)-5-(4-nitrophenyl)-pyrrole-2,3-dicarboxylate (6b)
Yellow powder, mp 148-150 ˚C. IR (KBr): ν_max = 1717 (C=O) cm^-¹. Anal. Calcd (%) for C₂₁H₁₈N₂O₆ (394.38): C, 63.96; H, 4.60; N, 7.10. Found: C, 63.67; H, 4.71; N, 7.29. ^¹H NMR (500 MHz, CDCl₃): δ = 2.24 (3 H, s, CH₃), 3.55 and 3.67 (6 H, 2 S, 2 OCH₃), 6.87 (1 H, s, CH pyrrol), 7.07 (4 H, m, arom.), 7.41 (2 H, d, J = 9 Hz, 2 CH arom.), 8.05 (2 H, d, J = 9 Hz, 2 CH arom.). ^¹³C NMR (500 MHz, CDCl₃): δ = 21.2 (CH₃), 52.2 and 52.5 (2 OCH₃), 120.6, 122.7, 123.9, 125.7, 126.2, 128.3, 129.7, 131.1, 136.4, 139.0, 140.1, 146.7 (arom.), 160.4, 166.7 (2 C=O, ester). MS: m/z (%) = 394 (100) [M⁺ ].

Di( tert -butyl) 1-(4-Methylphenyl)-5-(4-nitrophenyl)-pyrrole-2,3-dicarboxylate (6c)
Yellow oil. IR (KBr): ν_max = 1709 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₇H₃₀N₂O₆ (478.54): C, 67.77; H, 6.32; N, 5.85. Found: C, 67.92; H, 6.10; N, 5.97. ^¹H NMR (500 MHz, CDCl₃): δ = 1.31 (9 H, s, t-Bu), 1.48 (9 H, s, t-Bu), 2.41 (3 H, s, CH₃₎, 6.91 (1 H, s, CH pyrrole(, 7.19 (4 H, m, arom.), 7.58 and 8.20 (4 H, 2 d, ^³ J _HH = 8 Hz, arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 21.5 (CH₃), 28.2 and 28.4 (6 CH₃ of 2 t-Bu), 82.3 and 82.7 (2 C of 2 t-Bu), 121.5, 123.2, 124.0, 125.1, 126.2, 128.1, 129.2, 130.0, 137.5, 139.0, 141.4, 146.9 (arom.), 159.6 and 164.5 (2 C=O, ester). MS: m/z (%) = 478 (90) [M⁺ ].

Dimethyl 5-(4-Bromophenyl)-1-(4-methylphenyl)-pyrrole-2,3-dicarboxylate (6d)
Yellow oil. IR (KBr): ν_max = 1719 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₁H₁₈BrNO₄ (428.28): C, 58.89; H, 4.24; N, 3.27. Found: C, 58.97; H, 4.19; N, 3.55. ^¹H NMR (500 MHz, CDCl₃): δ = 2.41 (3 H, s, CH₃), 3.72 and 3.83 (6 H, 2 s, 2 OCH₃), 6.95 (1 H, s, CH pyrrole), 7.22 (4 H, m, 4 CH arom.), 7.30 (2 H, d, J = 9 Hz, 2 CH arom.), 7.49 (2 H, d, J = 9 Hz, 2 CH arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 21.6 (CH₃), 52.5 and 52.8 (2 OCH₃), 121.4, 121.6, 124.1, 124.4, 126.1, 126.2, 129.9, 130.0, 132.1, 132.7, 137.2, 139.1 (arom.), 160.9 and 166.8 (2 C=O, ester). MS: m/z (%) = 427 (95) [M⁺ ].

Diethyl 5-(4-Bromophenyl)-1-(4-methylphenyl)-pyrrole-2,3-dicarboxylate (6e)
Yellow oil. IR (KBr): ν_max = 1720 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₃H₂₂BrNO₄ (456.33): C, 60.54; H, 4.86; N, 3.07. Found: C, 60.29; H, 4.69; N, 3.31. ^¹H NMR (500 MHz, CDCl₃): δ = 1.17 and 1.30 (6 H, 2 t, ^³ J _HH = 7 Hz, 2 CH₃), 2.42 (3 H, s, CH₃), 4.16 and 4.31 (4 H, 2 q, ^³ J _HH = 7 Hz, 2 OCH₂)_, 6.93 (1 H, s, CH pyrrole), 7.22 (4 H, m, 4 CH arom.), 7.32 (2 H, d, J = 9 Hz, 2 CH arom.), 7.48 (2 H, d, J = 9 Hz, 2 CH arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.3, 14.6 and 21.6 (3 CH₃), 61.4 and 61.7 (2 OCH₂), 121.5, 121.6, 124.0, 124.5, 126.0, 126.3, 128.9, 130.2, 132.0, 132.8, 137.3, 139.0 (arom.), 160.4 and 166.3 (2 C=O, ester). MS: m/z (%) = 455 (77) [M⁺ ].

Dimethyl 1-(4-Methoxyphenyl)-5-(4-nitrophenyl)-pyrrole-2,3-dicarboxylate (6f)
Yellow powder; mp 159-161 ˚C. IR (KBr): ν_max = 1731, 1729 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₁H₁₈N₂O₇ (410.38): C, 61.46; H, 4.42; N, 6.83. Found: C, 61.52; H, 4.19; N, 7.07. ^¹H NMR (500 MHz, CDCl₃): δ = 3.73 and 3.85 (6 H, 2 s, 2 OCH₃), 3.86 (3 H, s, OCH₃), 7.05 (1 H, s, CH pyrrole), 6.95 (2 H, d, J = 8 Hz, 2 CH arom.), 7.28 (2 H, d, J = 8 Hz, 2 CH arom.), 7.60 (2 H, d, J = 8 Hz, 2 CH arom.), 8.22 (2 H, d, J = 8 Hz, 2 CH arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 52.6 and 52.9 (2 OCH₃), 56.0 (OCH₃), 114.6, 116.9, 120.9, 123.0, 124.3, 126.9, 127.6, 128.7, 132.2, 140.6, 147.1, 160.23 (arom.), 160.8 and 166.4 (2 C=O, ester). MS: m/z (%) = 410 (61) [M⁺ ].

Diethyl 5-(4-Bromophenyl)-1-(4-methoxyphenyl)-pyrrole-2,3-dicarboxylate (6g)
Yellow powder; mp 149-151 ˚C. IR (KBr): ν_max = 1714, 1711 (C=O, ester) cm^-¹. Anal. Calcd (%) for C₂₃H₂₂BrNO₅ (472.33): C, 58.49; H, 4.69; N, 2.97. Found: C, 58.25; H, 4.51; N, 3.11. ^¹H NMR (500 MH_Z, CDCl₃): δ = 1.16 and 1.27 (6 H, 2 t, ^³ J _HH = 7 Hz, 2 CH₃), 3.82 (3 H, s, OCH₃), 4.15 and 4.29 (4 H, 2 q, ^³ J _HH = 7 Hz, 2 OCH₂)_, 6.91 (1 H, s, CH pyrrole), 6.92, 7.24, 7.30 and 7.46 (8 H, 4 d, ^³ J _HH = 8 H_Z, arom.). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.3 and 14.5 (2 CH₃), 55.9 (OCH₃), 61.3 and 61.8 (2 OCH₂), 114.4, 116.9, 121.4, 123.8, 124.6, 126.2, 127.7, 129.9, 132.0, 132.7, 132.8 and 160.1 (arom.), 160.4 and 166.4 (2 C=O, ester). MS: m/z (%) = 471 (73) [M⁺ ].

Dimethyl 5-(4-Bromophenyl)-1-(4-chlorophenyl)-pyrrole-2,3-dicarboxylate (6h)
Yellow oil. IR (KBr): ν_max = 1718 (C=O) cm^-¹. Anal. Calcd (%) for C₂₀H₁₅BrClNO₄ (448.69): C, 53.54; H, 3.37; N, 3.12. Found: C, 53.20; H, 3.19; N, 3.35. ^¹H NMR (500 MHz, CDCl₃): δ = 3.72 and 3.84 (6 H, 2 s, 2 OCH₃), 6.94 (1 H, s, CH of pyrrole), 7.29 (4 H, m, 4 CH arom.), 7.42 (2 H, d, J = 9 Hz, 2 CH arom.), 7.50 (2 H, d, J = 9 Hz, 2 CH arom.). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 52.5 and 52.9 (2 OCH₃), 121.8, 122.3, 123.9, 124.5, 126.1, 127.9, 129.6, 129.8, 132.3, 132.6, 135.0, 138.2 (arom.), 160.6 and 166.7 (2 C=O, ester). MS: m/z (%) = 447 (37) [M⁺ ].