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: An expeditious synthesis of N -substituted pyrroles has been developed by reacting 2,5-dimethoxy tetrahydrofuran and several amines using a microwave-induced molecular iodine-catalyzed reaction under solventless conditions.


Introduction
Pyrroles are an important class of organic compounds with different types of medicinal activities [1,2], consequently, many methods for the synthesis of diversely substituted pyrroles have been developed [3].However, the most reliable method for the synthesis of pyrroles is the Paal-Knorr reaction [4,5].Because of the biological activities of our polyaromatic compounds [6][7][8][9][10], we became interested in the synthesis of pyrroles bound to the amines of different structures.We describe here a simple method of synthesis of N-substituted pyrroles by reacting 2,5-dimethoxytetrahydrofuran (1) and various amines in the absence of any solvent in a microwave oven in the presence of catalytic amounts (~5 mol%) of molecular iodine.This reaction produces pyrroles in excellent yield and within a short time under (Scheme 1).

Results and Discussion
This reaction has been tested by reacting different types of amines 2 and 2,5-dimethoxytetrahydrofuran in a microwave oven in the presence of molecular iodine as a catalyst.The reaction yields the products extremely well in the absence of any solvent.Reaction conditions and the yields of the products are shown in Table 1.Both aliphatic and aromatic amines produce pyrroles in very high yield.Importantly, the reaction produces product with multicyclic aromatic amines.A diamine (entry 9) and a heteropolyaromatic amine (entry 10) required higher temperature and longer reaction times, probably due to the diminished availability of the nitrogen (amine) lone pair.
We hypothesized that our work on iodine-catalyzed [11][12][13][14][15][16] reactions on acetal and glycosylation might prove useful for the facile synthesis of pyrroles under mild conditions.The methoxy groups in 2,5-dimethoxytetrahydrofuran (1) can be deprotected under mild acidic conditions and microwave irradiation.The intermediate can easily form the dialdehyde 5. On reaction with amines and the dialdehyde, pyrroles 3 can be prepared following a nucleophilic addition and subsequent dehydrationaromatization route (Scheme 2).After irradiating a CDCl 3 solution of 1 for 5 minutes, 1 H-NMR has been taken.A downfield signal due to the -CHO group is observed.The intensity of the -CHO group becomes more predominant in the 1 H-NMR when 1 was irradiated in CDCl 3 in the presence of catalytic amounts of iodine.This suggests the facile formation of dialdehyde 5 in the reaction media in the presence of iodine and microwave irradiation.The presence of small amount of iodine (~5 mol %) is essential for the success of the reaction.Table 1.Microwave-induced iodine-catalyzed synthesis of pyrroles.

General
Melting points were determined in a Fisher Scientific electrochemical Mel-Temp* manual melting point apparatus (Model 1001) equipped with a 300 °C thermometer.Elemental analyses (C, H, N) were conducted using the Perkin-Elmer 2400 series II elemental analyzer, their results were found to be in good agreement (± 0.2%) with the calculated values for C, H, N. FT-IR spectra were registered on a Bruker IFS 55 Equinox FTIR spectrophotometer as KBr discs. 1 H-NMR (300 MHz) and 13 C-NMR (75.4 MHz) spectra were obtained at room temperature with JEOL Eclipse-300 equipment using TMS as internal standard and CDCl 3 as solvent.Analytical grade chemicals (Sigma-Aldrich Corporation) were used throughout the project.Deionized water was used for the preparation of all aqueous solutions.

Conclusions
In summary, the present iodine-catalyzed microwave-induced method in the absence of any solvent is excellent for the preparation of N-substituted pyrroles (75-98% yields).Because of the simplicity of the procedure, products can be isolated very easily.The compounds reported herein will be tested against a number of cancer cells in vitro.