Task-Specific Basic Ionic Liquid: A Reusable and Green Catalyst for One-Pot Synthesis of Highly Functionalized Pyrroles in Aqueous Media

Abstract

A basic functionalized ionic liquid, 1-butyl-3-methylimidazolium hydroxide ([bmim]OH), catalyzed the three-component condensation reaction of acid chlorides, amino acids, and dialkyl acetylenedicarboxylates in water to afford functionalized pyrroles in high yields.

Key words

functional ionic liquid - pyrrole synthesis - aqueous media - green catalyst

References and Notes

• 1a Rantwijk F. Sheldon RA. Chem. Rev.  2007,  107:  2757 
• 1b Pârvulescu VI. Hardacre C. Chem. Rev.  2007,  107:  2615 
• 1c Chowdhury S. Mohan RS. Scott JL. Tetrahedron  2007,  63:  2363 
• 2a Binnemans K. Chem. Rev.  2007,  107:  2592 
• 2b Yavari I. Kowsari E. Tetrahedron Lett.  2007,  48:  3753 
• 3a Grieco PA. Organic Synthesis in Water   Blackie; London: 1998. 
• 3b Wei W. Li CJ. Varma RS. Clean Tech. Environ. Policy  2005,  7:  62 
• 3c Narayan S. Muldoon J. Finn MG. Angew. Chem. Int. Ed.  2005,  44:  3275 
• 4 Jacobi PA. Coults LD. Guo JS. Leung SI. J. Org. Chem.  2000,  65:  205 
• 5 For reviews on pyrrole synthesis, see: Sundberg RJ. In Comprehensive Heterocyclic Chemistry   Vol. 2:  Katritzky AR. Rees CW. Scriven EFV. Pergamon; Oxford: 1996.  p.119 
• 6 For examples of the Hantzsch synthesis, see: Trautwein AW. Süßmuth RD. Jung G. Bioorg. Med. Chem. Lett.  1998,  8:  2381 
• For recent examples of the Paal-Knorr synthesis, see:
• 7a Trost BM. Doherty GA. J. Am. Chem. Soc.  2000,  122:  3801 
• 7b Quiclet-Sire B. Quintero L. Sanchez-Jimenez G. Zard SZ. Synlett  2003,  75 
• 7c Tracey MR. Hsung RP. Lambeth RH. Synthesis  2004,  918 
• 8a Katritzky AR. Zhang S. Wang M. Kolb HC. Steel PJ. J. Heterocycl. Chem.  2002,  39:  759 
• 8b Bullington JL. Wolff RR. Jackson PF. J. Org. Chem.  2002,  67:  9439 
• 8c Washizuka KI. Minakata S. Ryu I. Komatsu M. Tetrahedron  1999,  55:  1296 
• 9 [bmim]OH was prepared according to literature, see: Ranu BC. Banerjee S. Org. Lett.  2005,  7:  3049 

10

Dimethyl 2,5-Diphenyl-1 H -pyrrole-3,4-dicarbox-ylate (4a); Typical Procedure
A solution of the benzoyl chloride (1a, 0.14 g, 1 mmol), phenyl glycine (2a, 0.15 g, 1 mmol), and [bmim]OH (1.40 g, 0.01 mol) in H₂O (2 mL) was stirred at r.t. for 15 min. Then, 3 (0.14 g, 1 mmol) was added and the reaction mixture was refluxed for 3 h (monitored by TLC). The reaction mixture was cooled to r.t. and the solid mass was filtered, washed with Et₂O, and crystallized from n-hexane-EtOAc to give 4a as colorless crystals; mp 150-151 °C; yield: 0.31 g (95%). IR (KBr): 3260 (NH), 1720 (C=O) cm^-1. ¹H NMR (500.1 MHz, CDCl₃): δ = 3.60 (s, 6 H, 2 OMe), 7.32-7.35 (m, 6 H, 6 CH), 7.50-7.52 (m, 4 H, 4CH), 8.85 (s, 1 H, NH). ¹³C NMR (125.7 MHz, CDCl₃): δ = 51.8 (2 OMe), 114.1 (2 C), 128.1 (2 CH), 128.5 (4 CH), 128.6 (4 CH), 130.8 (2 C), 137.8 (2 C), 165.8 (2 C=O). Anal. Calcd (%) for C₂₀H₁₇NO₄ (335.35): C, 71.56; H, 5.11; N, 4.18. Found: C, 71.70; H, 5.09; N, 4.21.
Dimethyl 2-Benzyl-5-phenyl-1 H -pyrrole-3,4-dicarbox-ylate (4e)
Colorless crystals; mp 134-135 °C; yield 0.32 g (92%). IR (KBr): 3252 (NH), 1728 (C=O) cm^-1. ¹H NMR (500.1 MHz, CDCl₃ ): δ = 3.80 (s, 3 H, OMe), 3.81 (s, 3 H, OMe), 4.30 (s, 2 H, CH₂), 7.24-7.37 (m, 10 H, 2 C₆H₅), 8.38 (s, 1 H, NH). ¹³C NMR (125.7 MHz, CDCl₃ ): δ = 32.9 (CH₂), 51.3 (OMe), 52.0 (OMe), 112.5 (C), 114.5 (C), 127.0 (CH), 127.1 (CH), 128.1 (2 CH), 128.7 (2 CH), 128.8 (2 CH), 128.9 (2 CH), 130.7 (C), 131.5 (C), 137.2 (C), 137.4 (C), 164.8 (C=O), 166.9 (C=O). Anal. Calcd (%) for C₂₁H₁₉NO₄ (349.38): C, 72.19; H, 5.48; N, 4.01. Found: C, 72.13; H, 5.51; N, 4.05. Dimethyl 2-Isobutyl-5-(4-methylphenyl)-1 H -pyrrole-3,4-dicarboxylate (4j)
Colorless crystals; mp 141-143 °C; yield 0.29 g (89%). IR (KBr): 3225 (NH), 1681 (C=O) cm^-1. ¹H NMR (500.1 MHz, CDCl₃): δ = 0.90 (d, ³ J = 7.2, 6 H, CHMe ₂), 1.92-1.97 (m, 1 H, CH), 2.32 (s, 3 H, Me), 2.70 (d, ³ J = 7.2 Hz, 2 H, CH₂), 3.77 (s, 3 H, OMe), 3.79 (s, 3 H, OMe), 7.11 (d, ³ J = 8.1 Hz, 2 H, 2 CH), 7.31 (d, ³ J = 8.1 Hz, 2 H, 2 CH), 8.87 (s, 1 H, NH). ¹³C NMR (125.7 MHz, CDCl₃): δ = 21.0 (Me), 22.2 (2 Me), 29.0 (CH), 35.6 (CH₂), 51.0 (OMe), 51.9 (OMe), 112.3 (C), 113.6 (C), 127.0 (2 CH), 128.0 (C), 129.2 (2 CH), 131.4 (C), 137.8 (C), 138.6 (C), 165.1 (C=O), 167.4 (C=O). Anal. Calcd (%) for C₁₉H₂₃NO₄ (329.39): C, 69.22; H, 7.00; N, 4.25. Found: C, 69.41; H, 7.03; N, 4.28.
All other compounds isolated possessed spectroscopic and analytical data in agreement with their proposed structures.