Potassium carbonate as a base for the N-alkylation of indole and pyrrole in ionic liquids Yogesh R. Jorapur, a Jae Min Jeong b and Dae Yoon Chi a, * a Department of Chemistry, Inha University, 253 Yonghyundong Namgu, Inchon 402-751, Republic of Korea b Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea Received 27 December 2005; revised 24 January 2006; accepted 27 January 2006 Available online 20 February 2006 Abstract—The methodology for the N-alkylation of indole and pyrrole using potassium carbonate in 1-n-butyl-3-methylimidazo- lium tetrafluoroborate [bmim][BF 4 ] as the sustainable reaction media with acetonitrile as the cosolvent is described herein. Our approach provides good yields with alkyl halides as well as sulfonates as the electrophiles. Cesium carbonate was also found to be a consistent base in the N-alkylation. The proposed methodology is simple and mild with easy workup. Ó 2006 Elsevier Ltd. All rights reserved. The need for indole and pyrrole research is well recog- nized because of their significance in the pharmaceutical area. 1 Naturally occurring substances with N-substi- tuted indole and pyrrole assemblies are ubiquitous, 2 as inhibitors of enzymes 3 or as anti-inflammatory, analge- sic, anti-rheumatic, and anti-hypertensive drugs. 4 N-Alkylated indole and pyrrole produced by regioselec- tive synthesis belong to an extremely attractive domain in heterocyclic chemistry as a result of their unusual bio- activities. One possible way of accomplishing the N-alkylation is by using a stoichiometric amount of a strong base. The established methods of accomplishing this include the use of alkali metals, 5 alkali metal alkox- ides, 6 or potassium hydroxide in DMSO, 7 potassium super oxide in crown ethers, 8 sodium hydroxide in DMF, 9 NaH or KH in DMF, 10 HMPA, 11 Cs 2 CO 3 in DMPU 12 and phase-transfer catalytic conditions. 13 Though some of the above-mentioned methods pro- vided good yields of N-alkylated indole and pyrrole, they also involve the use of hazardous and carcinogenic dipolar aprotic organic solvents. Moreover, during the workup, these solvents are converted into waste bypro- ducts, making their recycling impossible. Further, some of the above-mentioned bases possess a pungent or obnoxious odor. Thus, the development of an efficient, safe, and environmentally friendly method of accom- plishing the N-alkylation of indole and pyrrole consti- tutes an important challenge. In recent years, ionic liquids (ILs, Fig. 1), which are usu- ally composed of a bulky organic cation and a smaller inorganic anion, have emerged as a new, more sustain- able solvent system. 14 A wide range of reactions have been reported using ILs as the reaction media, 15 includ- ing alkylation reactions, for which the use of ILs have allowed for significant advances. 16 Also, recently we reported the selective C-alkylation of pyrrole at the C2 or C5 position using ILs as the smart sustainable reaction media. 17 During our studies on pyrrole C-alkylation in ILs with 1-bromo-3-phenylpropane (2a, 10 mol %), we obtained pyrrole carbamate 3 and N-alkylated pyrrole 4 as the minor byproducts. The same reaction in the absence of pyrrole provided symmetrical dialkylcarbonate 6 as the sole product. 18 These two observations diverted our attention toward the N-alkylation of pyrrole in ILs. In this work, we report on the N-alkylation of indole and pyrrole in ionic liquids using potassium carbonate as a base. The forma- tion of pyrrole carbamate 3 (Route A) and N-alkylated 0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2006.01.129 * Corresponding author. Tel.: +82 505 860 7686; fax: +82 32 867 5604; e-mail: dychi@inha.ac.kr N N X [bmim][X] {X = BF 4 , PF 6 , NTf 2 , OTf} Figure 1. Ionic liquids. Tetrahedron Letters 47 (2006) 2435–2438