Synlett 2014; 25(13): 1926-1936
DOI: 10.1055/s-0034-1378329
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Pentasubstituted Pyrroles via Catalyst-Free Multicomponent Reactions

Shaik Karamthulla
Department of Chemistry, Indian Institute of Technology Patna, Patna 800 013, Bihar, India   Fax: +91(612)2277383   Email: lokman@iitp.ac.in
,
Suman Pal
Department of Chemistry, Indian Institute of Technology Patna, Patna 800 013, Bihar, India   Fax: +91(612)2277383   Email: lokman@iitp.ac.in
,
Md. Nasim Khan
Department of Chemistry, Indian Institute of Technology Patna, Patna 800 013, Bihar, India   Fax: +91(612)2277383   Email: lokman@iitp.ac.in
,
Lokman H. Choudhury*
Department of Chemistry, Indian Institute of Technology Patna, Patna 800 013, Bihar, India   Fax: +91(612)2277383   Email: lokman@iitp.ac.in
› Author Affiliations
Further Information

Publication History

Received: 14 March 2014

Accepted after revision: 23 May 2014

Publication Date:
10 July 2014 (online)


Abstract

A facile and versatile catalyst-free method for the preparation of a wide range of pentasubstituted pyrroles has been reported using four-component reactions of arylglyoxal monohydrate, β-keto esters, amines, and various cyclic 1,3-dicarbonyls under mild reaction conditions. Employing this methodology, pseudo seven-component reactions have also been achieved in the case of p-phenylenediamine to provide conjugated bispyrroles with arene spacers.

Supporting Information

 
  • References and Notes

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  • 26 Synthesis of Ethyl 4-(4-Hydroxy-2-oxo-2H-chromen-3-yl)-2-methyl-1,5-diphenyl-1H-pyrrole-3-carboxylate (5a) – Typical Procedure A mixture of aniline (1 mmol) and ethyl acetoacetate (1 mmol) in EtOH (5 mL) was stirred for 1 h. To this solution 4-hydroxycoumarin (1 mmol) and phenylglyoxal monohydrate (1 mmol) were added, and the resultant mixture was stirred under reflux with progress of reaction being monitored by TLC. After completion of the reaction, the mixture was cooled to r.t., filtered, and the filtrate washed with cold EtOH. The resultant product was pure enough for characterization (88% yield); mp 146–148 °C. IR (KBr): 3161, 2977, 2366, 1694, 1616, 1559, 1538, 1500, 1458, 1370, 1299, 1198, 1174, 1134, 1092, 968, 759, 675, 588, 510 cm–1. 1H NMR (500 MHz, DMSO-d 6): δ = 10.77 (br s, 1 H, OH), 7.78 (d, J = 8.0 Hz, 1 H, ArH), 7.58 (t, J = 7.5 Hz, 1 H, ArH), 7.42 (d, J = 8.0 Hz, 1 H, ArH), 7.37 (t, J = 7.0 Hz, 1 H, ArH), 7.33 (d, J = 8.5 Hz, 1 H, ArH), 7.31–7.26 (m, 2 H, ArH), 7.23 (t, J = 8.0 Hz, 2 H, ArH), 7.08–7.03 (m, 3 H, ArH), 6.99 (d, J = 7.5 Hz, 2 H, ArH), 4.02–3.97 (m, 2 H, OCH2), 2.37 (s, 3 H, CH3), 0.93 (t, J = 7.5 Hz, 3 H, CH3). 13C NMR (125 MHz, DMSO-d 6): δ = 164.3, 161.9, 160.3, 152.2, 137.2, 136.8, 133.8, 131.7, 131.2, 129.5, 129.0, 128.2, 127.5, 127.0, 123.7, 123.3, 115.9, 115.8, 111.7, 111.6, 100.9, 58.5, 13.7, 12.6. Anal. Calcd for C29H23NO5 (465.50): C, 74.83; H, 4.98; N, 3.01. Found: C, 74.80; H, 4.96; N, 3.07. Synthesis of Diethyl 1,1′-(1,4-Phenylene)bis[4-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-methyl-5-phenyl-1H-pyrrole-3-carboxylate] (8a) – Typical Procedure A mixture of p-phenylenediamnie (1 mmol) and ethyl acetoacetate (2 mmol) in EtOH (5 mL) was stirred for 1 h. To this solution 4-hydroxycoumarin (2 mmol) and phenyl-glyoxal monohydrate (2 mmol) were added, and the resultant mixture was stirred under reflux conditions, progress of reaction being monitored by TLC. After completion of the reaction, the mixture was cooled to r.t., filtered, and the residue washed with cold EtOH. The resultant product 8a, obtained in 72% yield was pure enough for characterization; mp 259–261 °C. IR (KBr): 3278, 2974, 2345, 1699, 1616, 1517, 1404, 1300, 1265, 1208, 1173, 1093, 1050, 968, 898, 869, 758, 710, 667, 571 cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 10.75 (br s, 2 H, OH), 7.76 (d, J = 6.4 Hz, 2 H, ArH), 7.59–7.55 (m, 2 H, ArH), 734–7.29 (m, 8 H, ArH), 7.06–6.92 (m, 10 H, ArH), 3.99–3.98 (m, 4 H, OCH2), 2.35 (s, 6 H, CH3), 0.91 (t, J = 6.8 Hz, 6 H, CH3). 13C NMR (100 MHz, DMSO-d 6): δ = 164.6, 162.4, 160.7, 152.4, 137.2, 133.9, 132.1, 130.9, 129.5, 127.9, 127.4, 124.0, 123.5, 116.1, 112.2, 111.9, 100.9, 58.9, 13.9, 12.7. Anal. Calcd for C52H40N2O10 (852.88): C, 73.23; H, 4.73; N, 3.28. Found: C, 73.25; H, 4.77; N, 3.26.