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Synlett 2009(7): 1115-1117  
DOI: 10.1055/s-0028-1088224
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Novel Approach to the Synthesis of Highly Functionalized Pyrroles

Mohammad Anary-Abbasinejad*, Khadije Charkhati, Hossein Anaraki-Ardakani
Department of Chemistry, Islamic Azad University, Yazd Branch, P. O. Box 89195-155, Yazd, Iran
Fax: +98(351)8211109; e-Mail: mohammadanary@yahoo.com;
Further Information

Publication History

Received 2 January 2009
Publication Date:
20 March 2009 (online)

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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.

Key words

pyrrole derivatives - dialkyl acetylenedicarboxylates - triphenylphosphine - multicomponent reaction - intramolecular ­Wittig reaction

    References and Notes

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13

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.

14

Dimethyl 5-(4-Nitrophenyl)-1-(phenyl)-pyrrole-2,3-dicarboxylate (6a)
Yellow powder, mp 115-117 ˚C. IR (KBr): νmax = 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 MHZ, 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+ ].

15

Dimethyl 1-(4-Methylphenyl)-5-(4-nitrophenyl)-pyrrole-2,3-dicarboxylate (6b)
Yellow powder, mp 148-150 ˚C. IR (KBr): νmax = 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+ ].

16

Di( tert -butyl) 1-(4-Methylphenyl)-5-(4-nitrophenyl)-pyrrole-2,3-dicarboxylate (6c)
Yellow oil. IR (KBr): νmax = 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+ ].

17

Dimethyl 5-(4-Bromophenyl)-1-(4-methylphenyl)-pyrrole-2,3-dicarboxylate (6d)
Yellow oil. IR (KBr): νmax = 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+ ].

18

Diethyl 5-(4-Bromophenyl)-1-(4-methylphenyl)-pyrrole-2,3-dicarboxylate (6e)
Yellow oil. IR (KBr): νmax = 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+ ].

19

Dimethyl 1-(4-Methoxyphenyl)-5-(4-nitrophenyl)-pyrrole-2,3-dicarboxylate (6f)
Yellow powder; mp 159-161 ˚C. IR (KBr): νmax = 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+ ].

20

Diethyl 5-(4-Bromophenyl)-1-(4-methoxyphenyl)-pyrrole-2,3-dicarboxylate (6g)
Yellow powder; mp 149-151 ˚C. IR (KBr): νmax = 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 MHZ, 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 HZ, 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+ ].

21

Dimethyl 5-(4-Bromophenyl)-1-(4-chlorophenyl)-pyrrole-2,3-dicarboxylate (6h)
Yellow oil. IR (KBr): νmax = 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+ ].