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Synlett 2009(12): 1929-1932  
DOI: 10.1055/s-0029-1217516
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Synthesis of Functionalized 2,5-Dihydropyrrole Derivatives by Ph3P-Promoted Condensation between Acetylene Esters and α-Arylamino Ketones

Mohammad Anary-Abbasinejad*, Ehsanorreza Poorhassan, Alireza Hassanabadi
Department of Chemistry, Islamic Azad University, Yazd Branch, PO Box 89195-155, Yazd, Iran
Fax: +98(351)8211109; e-Mail: mohammadanary@yahoo.com;
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Publication History

Received 28 December 2008
Publication Date:
25 June 2009 (online)

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Abstract

A new and efficient one-pot synthesis of polysubstituted 2,5-dihydropyrrole derivatives by reaction between dialkyl acetylenedicarboxylates and β-aminoketones promoted by triphenyl­phosphine, is described. The prepared 2,5-dihydropyrroles can be easily oxidized to the corresponding pyrrole derivatives by chromium trioxide.

Key words

2,5-dihydropyrroles - dialkyl acetylenedicarboxylates - β-aminoketones - triphenylphosphine - intramolecular Wittig reaction

    References and Notes

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16

General procedure for the preparation of compounds 3a-h: To a magnetically stirred solution of β-aminoketone (1 mmol)­ and triphenylphosphine (0.28 g, 1 mmol) in CH2Cl2 (10 mL), was added dropwise a mixture of dialkyl acetylenedicar-boxylate (1 mmol) in CH2Cl2 (5 mL) at room temperature. The reaction mixture was stirred for 24 h, then the solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (hexane-EtOAc). The solvent was removed under reduced pressure to afford the product.
3a: White powder; mp 110-112 ˚C; IR (KBr): 1740, 1699 (ester) cm-¹; Anal. Calcd for C21H20BrNO5: C, 56.52; H, 4.52; N, 3.14. Found: C, 56.51; H, 4.33; N, 3.17; MS: m/z (%) = 445 (4); ¹H NMR (500 MHz, CDCl3): δ = 3.70, 3.73 and 3.75 (9 H, 3 × s, 3 × OCH3), 4.50 (1 H, dd, J = 15.7 Hz, J = 2.3 Hz, HCH), 4.72 (1 H, dd, J = 15.7 Hz, J = 6.5 Hz, HCH), 5.39 (1 H, dd, J = 6.5 Hz, J = 2.3 Hz, CH), 6.63 and 6.85 (4 H, 2 × d, J = 8.9 Hz, ArH), 7.35 and 7.55 (4 H, 2 × d, J = 8.4 Hz, ArH); ¹³C NMR (125.8 MHz, CDCl3): δ = 52.3, 52.9 and 56.2 (3 × OCH3), 61.3 (CH2), 70.3 (CH), 113.1, 115.6, 124.2, 125.3, 130.2, 131.8, 131.9, 140.1, 151.2 and 152.6 (aromatic and olefinic carbons), 163.5 and 172.1 (2 × CO ester). 3b: Viscose oil; IR (neat): 1726 (ester) cm-¹; Anal. Calcd for C23H24BrNO5: C, 58.24; H, 5.10; N, 2.95. Found: C, 58.10; H, 5.29; N, 2.78; MS: m/z (%) = 473 (11); ¹H NMR (500 MHz, CDCl3): δ = 1.20 (6 H, m, 2 × CH3), 3.73 (3 H, s, OCH3), 4.14 (4 H, m, 2 × OCH2), 4.77 (1 H, dd, J = 15.6 Hz, J = 2.3 Hz, HCH), 4.71 (1 H, dd, J = 15.6 Hz, J = 6.5 Hz, HCH), 5.38 (1 H, dd, J = 6.5 Hz, J = 2.3 Hz, CH), 6.66 and 6.85 (4 H, 2 × d, J = 9.0 Hz, 4 H, ArH), 7.36 and 7.52 (4 H, 2 × d, J = 8.5 Hz, ArH); ¹³C NMR (125.8 MHz, CDCl3): δ = 23.2 and 24.2 (2 × CH3), 55.9 (OCH3), 61.2, 61.3 and 61.7 (3 × OCH2), 70.4 (CH), 113.2, 115.5, 124.0, 126.2, 129.9, 130.3, 132.0, 140.1, 150.8 and 152.6 (aromatic and olefinic carbons), 162.9 and 171.7 (2 × CO ester). 3c: White powder; mp 114-116 ˚C; IR (KBr): 1735, 1709 (ester) cm-¹; Anal. Calcd for C21H20ClNO5: C, 62.77; H, 5.02; N, 3.49. Found: C, 62.91; H, 5.17; N, 3.33; MS: m/z (%) = 401 (27); ¹H NMR (500 MHz, CDCl3): δ = 3.51, 3.54 and 3.57 (9 H, 3 × s, 3 × OCH3), 4.33 (1 H, dd, J = 15.6 Hz, J = 2.4 Hz, HCH), 4.53 (1 H, dd, J = 15.6 Hz, J = 6.4 Hz, HCH), 5.21 (1 H, dd, J = 6.4 Hz, J = 2.4 Hz, CH), 6.45 and 6.68 (4 H, 2 × d, J = 8.8 Hz, ArH), 7.18-7.25 (4 H, m, C6H4Cl); ¹³C NMR (125.8 MHz, CDCl3): δ = 51.8, 52.4 and 52.7 (3 × OCH3), 60.9 (CH2), 69.9 (CH), 112.7, 115.2, 124.8, 128.5, 129.6, 131.0, 135.5, 139.8, 150.8 and 152.2 (aromatic and olefinic carbons), 163.1 and 173.7 (2 × CO ester). 3d: Viscose oil; IR (neat): 1730, 1710 (2 × CO ester) cm-¹; Anal. Calcd for C23H24ClNO5: C, 64.26; H, 5.63; N, 3.26. Found: C, 64.20; H, 5.54; N, 3.37; MS: m/z (%) = 429 (25); ¹H NMR (500 MHz, CDCl3): δ = 1.01, 1.04 (6 H, 2 × t, J = 7.4 Hz, 2 × CH3), 3.51 (4 H, m, 2 × OCH2), 3.57 (3 H, s, OCH3), 4.32 (1 H, dd, J = 15.6 Hz, J = 2.4 Hz, HCH), 4.53 (1 H, dd, J = 15.6 Hz, J = 6.4 Hz, HCH), 5.20 (1 H, dd, J = 6.4 Hz, J = 2.4 Hz, CH), 6.45 and 6.67 (4 H, 2 × d, J = 8.8 Hz, C6 H 4OCH3), 7.18-7.26 (4 H, m, C6H4Cl); ¹³C NMR (125.8 MHz, CDCl3): δ = 14.1 and 14.2 (2 × CH3), 55.4 (OCH3), 60.8, 60.9 and 61.3 (3 × CH2), 68.2 (CH), 112.8, 114.2, 115.1, 122.6, 125.3, 128.4, 129.7, 131.2, 135.3, 139.7, 150.4 and 152.1 (aromatic and olefinic carbons), 162.6 and 171.5 (2 × CO ester). 3e: Viscose oil; IR (neat): 1734, 1715 (2 × CO ester) cm-¹; Anal. Calcd for C27H32ClNO5: C, 66.73; H, 6.64; N, 2.88. Found: C, 66.91; H, 6.61; N, 2.73. MS: m/z (%) = 485 (9); ¹H NMR (500 MHz, CDCl3): δ = 1.19 and 1.21 (18 H, 2 × s, 6 × CH3), 4.25 (1 H, dd, J = 15.6 Hz, J = 2.4 Hz, HCH), 4.45 (1 H, dd, J = 15.6 Hz, J = 6.4 Hz, HCH), 5.05 (1 H, dd, J = 6.4 Hz, J = 2.4 Hz, CH), 6.45 and 6.66 (4 H, 2 × d, J = 9.0 Hz, C6 H 4OCH3), 7.00-7.20 (4 H, m, C6 H 4Cl); ¹³C NMR (125.8 MHz, CDCl3): δ = 27.9 and 29.8 (6 × CH3), 55.6, 55.7 (2 × OCH3), 60.7 (CH2), 71.1 (CH), 81.4 and 81.8 (2 × OC), 112.9, 115.0, 124.5, 127.2, 128.6, 129.5, 131.4, 134.9, 139.9, 147.8 and 151.9 (aromatic and olefinic carbons), 161.9 and 171.8 (2 × CO ester). 3f: Viscose oil; IR (KBr): 1733, 1711 (ester) cm-¹; Anal. Calcd for C21H21NO5: C, 68.65; H, 5.76; N, 3.81. Found: C, 68.88; H, 5.66; N, 3.94. MS: m/z (%) = 367 (23). ¹H NMR (500 MHz, CDCl3): δ = 3.50, 3.57 and 3.59 (9 H, 3 × s, 3 × OCH3), 4.36 (1 H, dd, J = 15.6 Hz, J = 2.4 Hz, HCH), 4.58 (1 H, dd, J = 15.6 Hz, J = 6.4 Hz, HCH), 5.23 (1 H, dd, J = 6.4 Hz, J = 2.4 Hz, CH), 6.48 and 6.62 (4 H, 2 × d, J = 8.8 Hz, ArH), 7.23-7.55 (5 H, m, C6H5); ¹³C NMR (125.8 MHz, CDCl3): δ = 51.2, 52.4 and 52.7 (3 × OCH3), 60.8 (CH2), 69.9 (CH), 113.7, 115.8, 124.3, 124.9, 128.5, 129.1, 131.0, 139.8, 150.7 and 151.9 (aromatic and olefinic carbons), 163.1 and 173.7 (2 × CO ester). 3g: Viscose oil; IR (neat): 1735, 1707 (ester) cm-¹; Anal. Calcd for C21H21NO4: C, 71.78; H, 6.02; N, 3.99. Found: C, 71.70; H, 5.78; N, 3.72; MS: m/z (%) = 351 (31); ¹H NMR (500 MHz, CDCl3): δ = 2.33 (3 H, s, CH3), 3.66 and 3.71 (6 H, 2 × s, 2 × OCH3), 4.57 (1 H, dd, J = 15.8 Hz, J = 2.3 Hz, HCH), 4.76 (1 H, dd, J = 15.8 Hz, J = 6.4 Hz, HCH), 5.45 (1 H, dd, J = 6.4 Hz, J = 2.3 Hz, CH), 7.23-7.59 (9 H, m, ArH). ¹³C NMR (125.8 MHz, CDCl3): δ = 21.6 (CH3), 52.2, 52.9 (2 × OCH3), 61.0 (CH2), 70.0 (CH), 112.2, 124.5, 127.2, 128.5, 128.6, 128.9, 129.9, 130.5, 143.5, 152.3 (aromatic and olefinic carbons), 164.3, 172.4 (2 × CO ester). 3h: Viscose oil; IR (neat): 1732, 1695 (ester) cm-¹; Anal. Calcd for C20H18ClNO4: C, 64.61; H, 4.88; N, 3.77. Found: C, 64.79; H, 4.80; N, 3.90; MS:
m/z (%) = 371 (27); ¹H NMR (500 MHz, CDCl3): δ = 3.69 and 3.74 (6 H, 2 × s, 2 × OCH3), 4.55 (1 H, dd, J = 15.7 Hz, J = 2.0 Hz, HCH), 4.75 (1 H, dd, J = 15.7 Hz, J = 6.2 Hz, HCH), 5.41 (1 H, dd, J = 6.2 Hz, J = 2.0 Hz, CH), 6.61 and 7.2 (4 H, 2 × d, J = 8.9 Hz, C6 H 4Cl), 7.40-7.48 (5 H, m, C6H5); ¹³C NMR (125.8 MHz, CDCl3): δ = 52.2 and 53.0 (2 × OCH3), 60.9 (CH2), 70.0 (CH), 113.3, 115.7, 123.1, 124.4, 128.5, 128.6, 129.8, 130.0, 144.2 and 151.0 (aromatic and olefinic carbons), 163.5 and 171.7 (2 × CO ester).

23

General procedure for the preparation of compounds 7a-c: To a magnetically stirred solution of dihydropyrrole derivative 3 (1 mmol) in CHCl3 (10 mL), was added CrO3 (1 mmol) at room temperature. The reaction mixture was stirred for 4 h, then the solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (hexane-EtOAc). The solvent was removed under reduced pressure to afford the product.
7a: White powder; mp 123-125 ˚C; IR (KBr): 1740, 1707 (ester) cm-¹; Anal. Calcd for C21H19NO5: C, 69.03; H, 5.24; N, 3.83. Found: C, 69.31; H, 5.19; N, 3.89; MS: m/z (%) = 365 (34); ¹H NMR (500 MHz, CDCl3): δ = 3.76, 3.86, 3.88 (9 H, 3 × s, 3 × OCH3), 6.98 and 7.30 (4 H, 2 × d, J = 9.0 Hz, ArH), 7.10 (1 H, s, CH of pyrrole), 7.28-7.45 (5 H, C6H5); ¹³C NMR (125.8 MHz, CDCl3): δ = 52.3, 55.9 and 56.2 (3 × OCH3), 114.4, 121.9, 123.8, 125.0, 126.7, 127.5, 127.8, 128.1, 129.9, 132.8, 133.7 and 159.9 (aromatic and olefinic carbons), 160.9 and 167.2 (2 × CO ester). 7b: Viscose oil; IR (KBr): 1740, 1707 (ester) cm-¹; Anal. Calcd for C21H19NO4: C, 72.19; H, 5.48; N, 4.01. Found: C, 72.40; H, 5.29; N, 4.09; MS: m/z (%) = 349 (19); ¹H NMR (500 MHz, CDCl3): δ = 2.42, 3.73, 3.85 (9 H, 3 × s, 3 × CH3), 6.64 and 7.10 (4 H,
2 × d, J = 8.4 Hz, C6 H 4CH3), 6.99 (1 H, s, CH of pyrrole), 7.23-7.59 (5 H, m, C6H5); ¹³C NMR (125.8 MHz, CDCl3):
δ = 20.7, 52.4 and 52.8 (3 × CH3), 121.9, 123.7, 125.1, 126.3, 126.4, 127.6, 128.1, 129.0, 130.0, 133.0, 133.6, 137.4 (aromatic and olefinic carbons), 160.9, 167.2 (2 × CO ester). 7c: Viscose oil; IR (neat): 1712, 1743 (ester) cm-¹; Anal. Calcd for C21H18BrNO5: C, 56.77; H, 4.08; N, 3.15. Found: C, 56.90; H, 4.22; N, 3.39; MS: m/z (%) = 443 (24); ¹H NMR (500 MHz, CDCl3): δ = 3.77, 3.83, 3.81 (9 H, 3 × s, 3 × OCH3), 6.99 and 7.29 (4 H, 2 × d, J = 9.1 Hz, ArH), 7.15 (1 H, s, CH of pyrrole), 7.47 and 7.63 (4 H, 2 × d, J = 8.3 Hz, ArH); ¹³C NMR (125.8 MHz, CDCl3): δ = 52.3, 56.1 and 56.4 (3 × OCH3), 113.1, 121.9, 123.8, 125.7, 126.7, 127.8, 130.2, 131.0, 131.7, 132.8, 133.6, 159.2 (aromatic and olefinic carbons), 160.8, 167.2 (2 × CO ester).