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.

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 

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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.